HTP-APP_Attach 1_Technical Brief.pdf

Request for Interest (RFI) HTP-APP Technical Brief

1.0 Purpose/Scope

The purpose of this appendix is to outline the technical requirements for the High-throughput

Automated Phenotyping Platform (HTP-APP), which is the primary portion of the Microbial Molecular

Phenotyping Capability (M2PC) project, Request for Proposal (RFP). The information within this appendix is not all inclusive and is subject to change in the actual RFP. It is to be used as a guide to help answer the questions presented in the RFI.

The minimum technical performance requirements for a vendor experienced in the field to manage and execute the design, fabrication, installation, testing, and training the HTP-APP will be included in a detailed performance specification (P-Spec) within the RFP.

2.0 Scope

The contractor will be required to provide a fully functional system and demonstrate that the HTP-APP will achieve the project Key Performance Parameters (KPPs) as shown in Table 2.1. The HTP-APP system shall be installed and tested at a newly constructed facility at PNNL.

Table 2.1: Project Key Performance Parameters

The contractor will be required to deliver a system that includes hardware, equipment, and the software necessary to achieve these KPPs. An extensive description of the KPPs, and exemplar use cases, will be defined within the P-Spec. The contractor or vendor, which may include a team of vendors to deliver the

HTP-APP, will deliver the system with the following major milestones:

1. System Design

a. 30% Design package

b. 60% Design package (coincides with Design Commitment)

c. 90% Design package

d. Final Design package

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.

2. System Assembly

3. Factory Testing

4. Installation at the M2PC facility

5. Software installation

6. Connection to the facility Lab Information Management System (LIMS)

7. Functional testing after installation, including KPP verification

8. Training PNNL staff to operate, maintain, and modify the physical system and software

The scope is graphically depicted in the following figure:

3.0 Stretch Goals

The P-Spec will be structured for the contractor (or contractor team) to deliver the minimum requirements that meet the minimum KPPs. However, the project team has included a maximum contract price, that we believe enables throughput values greater than the minimum KPPs. The contractor will be asked to pursue stretch goals and scope, within the contract budget to maximize the best value to the project. In order of preference, the following stretch goals should be considered for inclusion in the offeror’s proposal. The stretch goals will be defined in greater detail in the official performance specification.

1. Exceed both Threshold KPP#1 and KPP#2 by approximately 25%.

2. Exceed both Threshold KPP#1 and KPP#2 by approximately 50%.

3. Exceed both Threshold KPP #1 and KPP#2 up to:

a. KPP#1 (i): 2,000 strain experiments per week.

b. KPP#1(ii): 500 microbiome experiments per week.

c. KPP#2: 3,000,000 multimodal analytical measurements per month.

4. Process and Development Lab fit out.

4.0 Facility Coordination

The HTP-APP will be installed and reside in a newly constructed facility that is comprised of laboratory and support space in a new expansion to the existing Environmental Molecular Sciences Laboratory (EMSL). EMSL is a DOE Office of Science Biological and Environmental Research scientific user facility on the Pacific Northwest National Laboratory campus (PNNL). The new facility will be designed and built by a construction contractor in parallel with the HTP-APP contract. The facility will include laboratory spaces, functions, systems, and support spaces to house and operate the HTP-APP. The HTP-APP contractor is not responsible for delivering the facility or utilities from the facility; however, the automation contractor shall coordinate their design, utility needs, installation and locations, and delivery schedule with the facility contractor. A partnering attitude and approach with PNNL and the facility contractor are required to deliver a successful project.

The line of demarcation for the installation is tentatively defined such that the HTP-APP contractor will be responsible for the final utility connections to HTP-APP equipment. The facility contractor will bring utilities (e.g., electrical, exhaust, vacuum, compressed air, nitrogen, chilled water) to within approximately 5’ of the equipment. It is anticipated that all electrical connections will be cord and plug, and mechanical connections will be Swagelok, NPT fittings, or similar. The HTP-APP contractor would make final connections using flexible tubing and the appropriate fitting.

5.0 Design Requirements

The HTP-APP contractor, with its extensive research and high-throughput automated phenotyping equipment knowledge and expertise, will use the technical requirements defined within the performance specification to develop a complete final design package in collaboration with Battelle staff. This will include coordination with the facility design-build contractor for the location of and types of utility connection points necessary in the automation laboratory and support spaces. Design packages will require review and approval by PNNL and the DOE, including the project team, subject matter experts, and applicable authorities having jurisdiction.

5.1 Design Commitment

The system throughput values included in the offeror’s proposal (minimum base requirements plus stretch goals) are the foundation for the system design and contract award; however, it is understood that the exact equipment types and numbers of equipment to achieve the proposed system throughput values could change with further design development after the proposal. Therefore, to allow for design maturation and flexibility, the project will require design commitment from the HTP-APP contractor coincident with the 60% design package. Design commitment means that the features of work submitted in the 60% design package conforms to the contractor’s budget, schedule, and the quality requirements of the contract. The contractor commits that the system and associated equipment will be delivered as detailed within the 60% design package. Design Commitment occurs upon the submission, by the HTP-APP vendor, of the 60% design package as detailed in Appendix A, and as approved by the Battelle Contracts Specialist. Reductions in scope, form, fit, finish, or quality after Design Commitment has been achieved, shall not be permitted unless expressly approved, in writing, by the Battelle Contracts Specialist.

The 60% design package, including outstanding comments made during the 30% and 60% design package reviews, forms the Basis of Design.

The Basis of Design (BOD) is a document that outlines the assumptions, rationale, criteria, and principles used in calculations and decisions during a project's design. It's the foundation for the design and construction process, and guides the design team's decision-making from the initial concept to the final construction documents. The BOD aims to establish a common understanding of the project's goals, scope, and expectations among all parties involved.

U.S. Department of Energy defines Design basis as "Information that identifies the specific functions to be performed by a structure, system, or component of a facility, and the specific values or range of values chosen for controlling parameters as reference bounds of Design. These values may be (1) restraints derived from generally accepted "state of the art" practices for achieving functional goals, or

(2) requirements derived from analyses (based on calculations and/or experiments) of the effects of a postulated accident for which a structure, system, or component must meet its functional goals."

6.0 Project Management and Execution

The contractor will be required to develop a project management plan detailing the proposed project execution for approval by Battelle. This will include a schedule based upon the information herein:

Proposed Project Schedule https://gcc02.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.directives.doe.gov%2Fterms_definitions%2Fdesign-basis%23%3A~%3Atext%3DInformation%2520that%2520identifies%2520the%2520specific%2Cas%2520reference%2520bounds%2520of%2520design.&data=05%7C02%7Csamantha.ernst%40pnnl.gov%7C7caaa7c8b966407ad6a508dc75d35710%7Cd6faa5f90ae240338c0130048a38deeb%7C0%7C0%7C638514797757041756%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=%2Bc1W%2B%2FlYhTXpXZmDEzjXRsOqHEP5jGcziPIWKGwu5d0%3D&reserved=0

Once the contract is awarded to the HTP-APP contractor (or contractor team), the contractor shall use the above schedule as a framework to develop an integrated schedule with the facility design-build contractor. This schedule will be indexed on the design-build contractor “ready for equipment” milestone in the automation laboratory. The HTP-APP contractor will not be able to deliver and begin the installation of the equipment in the facility until this facility contractor milestone is accomplished.

The HTP-APP shall be executed in multiple tasks as described in the performance specification.

Modifications to the timing and type of the design, procurement, assembly, testing, and training tasks can be proposed by the HTP-APP contractor to maximize efficient project execution. A proposed modification to the defined timing and deliverable description is subject to Battelle review and approval and there are no guarantees that a modification will be approved.

Equipment purchases will be executed to accommodate funding profile similar to the one presented below. The funding will likely be constrained due to congressional appropriation.

Proposed Funding Profile for HTP-APP Contractor

FY25 FY26 FY27 FY28 FY29+

$2M $6.5M $25M $10M Balance of Contract

7.0 Science Core Functions

Refer to Appendix A, for a description of the 5 science core functions that are required to be included with the HTP-APP.

8.0 General System Requirements

In addition to the specific requirements for each science core function of the HTP-APP, the system shall:

• Be designed to maximize the throughput, efficiency, overall capability uptime and sample uniformity while incorporating sample tracking and capturing of read and meta data for the capability.

• Be modular and customizable through the addition or removal of individual components.

o Addition or removal of a component shall minimize overall system downtime. The timeframe shall be accomplishable in hours to days with minimal system training and no impact to operations of the remainder of the system.

o Addition or removal of a component shall minimize impacts to the operation of instruments in the system.

o Accommodate rapid advances in technology to easily expand the flexible system, integrate emerging technologies and adapt to new workflows.

o Include integrated experimental systems in a modular and flexible manner and shall be able to conduct entire workflows without human intervention to the greatest extent possible.

o Be designed to enable integration of new instruments with only minor updates and at minimal expense. In addition, a modular approach to hardware design must allow system architects to quickly retire old instruments and replace them with new ones (with equivalent or different functions), which in turn facilitates easy adoption of emerging technologies.

• The capability shall provide for longevity by utilizing modular and easily expandable/interchangeable automation technologies that account for future analytical instrument developments as much as possible and with provisions to efficiently incorporate new technologies.

• Maintain experimental customizability while maximizing the throughput by optimizing other parameters including modularity, flexibility, automation, scalability, and expandability of cutting-edge instruments.

• Be designed for maximal safety, ergonomics, modularity, and serviceability, including during inclusion of new instrument incorporation.

• Be equipment vendor non-specific and be able to incorporate instruments from multiple vendors.

• Be redundant in that no single point of equipment or instrument failures would stop system operations. For example, if a plate reader becomes non-operational, a redundant piece of equipment would maintain the capability to operate the entire system.

• Minimize non-flexible backbone or system components.

9.0 System Characteristics

The system will be required to have the following characteristics and/or deliverables. They will be defined in detail in the performance specification:

o 5 Science Core Functions o Remote Planning and Operation o Scheduling Software, which will likely have multiple layers.

o Other Software required to make the platform fully functional.

o Safety Requirements o BSL-2, for certain portions of the system o Robotics, which will require intrinsically safe design.

o Electrical safety, which will require that the systems are NRTL certified.

o Design and installation coordination with the facility contractor.

o System Training o Factory Testing, which will likely have to be iterative.

o On-Site Functional Testing, which will likely have to be iterative and include steps from small scale testing to larger scale testing as the system is assembled.

o KPP Verification, specific testing that verifies the KPPs included in the proposal have been achieved.

o On-site 3rd party commissioning. Battelle will hire a 3rd party to ensure that the testing is performed in accordance with the agreed test procedures and that the test results are verifiable and repeatable.

o Training o A list of consumables o A minimum amount of redundant automation hardware for spares.

APPENDIX A

Science Core Functions of the High Throughput Automated Phenotyping Platform (HTP-APP)

The Department of Energy (DOE) is interested in developing a modular and flexible automated microbial molecular phenotyping capability (M2PC). The scope of this project includes the acquisition, installation, and commissioning of high throughput (HTP) automation equipment and analytical instrumentation necessary to execute the mission need in a newly constructed laboratory space on the Pacific Northwest

National Laboratory (PNNL) campus. The high throughput automated phenotyping platform (HTP-APP) is an end-to-end automated platform that enables researchers to investigate strain engineering and microbial function under a wide variety of dynamic microbial growth conditions and analyze these using a variety of analytical methods with minimal need for operator intervention. The complete system will allow for maximum modularity, flexibility, and expandability. It will be installed and reside in a facility that is comprised of laboratory and support space in a new expansion to the existing Environmental

Molecular Sciences Laboratory (EMSL) which is a DOE Office of Science Biological and Environmental

Research program user facility on the PNNL campus.

The new M2PC will address the following three needs: (1) closing the gap on the ability to annotate/predict the function of every protein in single organisms, including importantly current chassis/model organisms, while looking to expand the list of model organisms with full annotation

(including complete transcriptional, proteomic and metabolomic profiles for individual organisms); (2) accelerate the Design-Build-Test-Learn cycle by a factor of 10x to speed the discovery of new/unknown functions; and (3) understand key microbe and microbial consortia interactions that confer beneficial communal function and fitness (i.e. cultivability, stress resistance, increased productivity). To meet these needs, we identified incorporation of five distinct but intimately connected science core functions; (i) media, (ii) cultivation, (iii) sample preparation, (iv) strain engineering and (v) functional assaying/multimodal analysis which are the important components of the HTP-APP. These five science core functions are briefly described in the following sections.

Science Core Function #1 – Media:

• Bulk media or bulk media components will be formulated by hand outside the M2PC system and needed amount can be transferred to the media science core function capability in M2PC.

• Offline capabilities shall include supplement addition, subsequent storage, transfer of appropriate media under experimental conditions.

• The media dispensing capability in M2PC system should have the ability to explore a wide parameter space of media conditions.

• The media dispensing capability should have the ability to use SBS format plates and tube racks with up to total of 1 mL volume.

• Media dispensing capability in M2PC system should have both the ability to bulk dispense a single media type into many plates and different media type and composition to every well or every plate.

• Bottles of fully prepared media, or media components could be placed on the media dispensing capability, and the system could then dispense media into the correct plates and wells based on the experimental needs.

• The media dispensing capability in M2PC system should house a waste processing device, which will be the main location where waste will be collected from the system. The waste collection should include solid and solvent waste collection capabilities.

• The media dispensing capability in M2PC system should have the following features:

- ability to blend different media composition from at least 12 independent media or media component sources into individual wells in the sample plates (different volume of each input).

- ability to affix barcodes to 4000 consumables/week.

- ability to wash and dry 1000 tip boxes/week.

- ability to store at least 600 tip boxes and 600 plates simultaneously.

- ability to dispense 5uL-1500uL media/well into 1000 96 well plates/week.

- seal all plates with breathable or solid seals.

- ability to sort system waste by separating liquid waste streams and removing solvents from plates and strong in waste canisters.

- ability to store solid wastes,

- tips ready for disposal are separated from their recyclable bases.

- waste sorting for BSL-2 workflows needs to be separated and stored within a BSL-2 controlled enclosures.

Science Core Function #2 – Cultivation:

• M2PC cultivation capability should include a large bank of incubators to grow organisms in and should also include equipment to inoculate plates.

• M2PC cultivation capability has the ability to 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.

• In M2PC cultivation capability, some portions of cultivation equipment need to be offline to provide the capacity and experimental conditions needed to satisfy multiday cultivations using a combination of offline and online capabilities during varying times to avoid inefficiencies. At least, 1/3 of the capability or more should be fully integrated with the automation system.

• The cultivation capability should have the ability to use SBS format plates and tube racks with up to total of 1 mL volume.

• The location of an individual plate both between and within incubators shall be tracked so that an individual plate can be removed at a given time, based on experimental needs.

• The cultivation capability should have a colony picker to transfer colonies on solid substrates such as agar plates or biofilms to liquid media or other solid substrates.

• M2PC cultivation system should have the ability to monitor growth kinetics without disturbing the physiology.

• M2PC cultivation system should have the ability to remove a plate from an incubator, measure the optical density (OD), and return the plate to an incubator within 10 minutes or have some capacity for real-time ODs so that growth kinetics can be observed without disturbing the physiology.

• In M2PC capability, BSL-2 controlled organisms will need to be inoculated within appropriate physical containment.

• The cultivation capability in M2PC system should have the following features:

- ability to simultaneously cultivate 500 medium well plates SBS format plates and tube racks.

- ability to inoculate 750 plates/week.

- ability to inoculate with volume ranges from 5 to 250 microliters.

- ability to centrifuge the liquid if necessary.

- ability to seal the plates with gas permeable seals after inoculation.

- ability to provide orbital shaking with up to a 3mm throw and be able to shake up to

1000rpm.

- ability to provide temperature control between 4C and 45C with humidity control.

- ability to provide gas control between O2 and CO2.

- ability to provide controllable illumination preferably with proper mitigation of heat transfer to the cultivation plates.

- ability to locate and track an individual plate both between and within incubators so that an individual plate can be removed at a given time, based on experimental needs.

Science Core Function #3 – Sample Preparation:

• The M2PC sample preparation capability should accommodate wide range of sample preparation techniques to satisfy the sample requirements for a wide range analytical techniques.

• The M2PC sample preparation capability requires both capabilities common to most sample preparations (stamping, sealing, and bulk dispensing reagents) and also capabilities with lower usage, but that expand the landscape of possible analytical techniques.

• Many of the techniques used during sample preparation can produce splashes and aerosols and should therefore be contained within BSL-2 controlled physical biological containment while sample preparation techniques that don’t form aerosols can be kept outside the BSL-2 enclosures.

• The sample preparation capability in M2PC system should have the following features:

- ability to seal 3500 plates/week.

- ability to perform 3500 stamps/week with transfer volumes of 5-250uL.

- ability to perform hit-picks/cherry-picks (well to well transfers, rather than full plate transfers)

- ability to peel 3500 plates/week.

- ability to bulk dispense solvent/buffer into 3500 plates/week selecting from at least 6 solvents/buffer with 50-1000uL dispense volume.

- ability to centrifuge 2000 plates/week,

- ability to shake plates.

- ability to support enzymatic reactions, there should be capacity to statically incubate plates with at least 3 temperature options.

- ability to provide (i) Bead Beater, with ability to add automatically add metal beads to a plate, (ii) Positive pressure device, (iii) Sample concentrator, (iv) Fraction Collector and (v)

Well-based stirring to mix up individual wells of a plate capabilities (consider having >1 device if the device is slow).

- ability to perform sample preparation for various offline capabilities including NMR, high field FTIR MS, and cryo electron microscopy.

- ability to lyophilize plates as an integrated automation or offline capability.

Science Core Function #4 – Strain Engineering:

• M2PC Strain Engineering capability should be able to do each transformation attempt, e.g. a single well of a plate, represents the start of building a new microbial strain with a unique genome.

• M2PC Strain Engineering capability should accommodate transfer volume ranges from 5 to 250 microliters.

• M2PC Strain Engineering capability should be able to create each combination of one or more unique microbes in varying conditions.

• The strain engineering capability in the M2PC system should have the following features:

- ability to seal, peel and stamp plates with breathable or solid seals after dispensing.

- ability to perform heating and shaking.

- ability to perform thermocycling using automation-compatible thermocyclers to support strain build and for cell lysis before DNA extraction.

- ability to perform liquid handling using a special liquid handler to support nanoliter volume hit picking required to set up PCR reactions in addition to the other liquid handlers to meet the requirements.

- some of the additional instruments which need to be integrated are the following: colony picker, incubator space, -20C plate storage, late peelers, plate sealers, plate readers, centrifuges and liquid handlers

- some of the additional instruments which need to be offline are the following: sequencer and microfluidic strain build box.

Science Core Function #5 – Analytical Capabilities:

• M2PC system shall provide HTP assaying of optical, morphological, physiological, and biochemical properties of organisms. The complete system shall be equipped with enough multiple analytical capabilities that are integrated into the HTP-APP to meet the KPPs.

• M2PC analytical capabilities should include integrated automated various mass spectrometry capabilities, including GC-MS and LC-MS, and ICP-MS instruments to allow for proteomic, lipidomic, and metabolomic workflows for a diverse set of molecules.

• M2PC analytical capabilities should also include some more state-of-the-art mass spectrometry capabilities including integrated automated MALDI (matrix assisted laser desorption/ionization) mass spectrometry to support soil microbe research and biofilm research and allow the spatial analysis of metabolites and proteins, Trapped Ion Mobility Spectroscopy (a.k.a., TIMS Tof), Orbitrap, Triple quadrupole MS and Quadrupole time of flight (a.k.a., Q – ToF).

• M2PC analytical capabilities should include integrated automated high-throughput chromatography with GC-FIDs for the analysis of volatiles and other molecules and LC-UVs for chromatography.

• M2PC analytical capabilities should include integrated automated LC-UVs which should be able to handle 1200 Barr of pressure or higher and at least one of these LCs should be equipped with refractive index (RI) detector.

• M2PC analytical capabilities should include automated microscopy/imaging capabilities to analyze cells.

• M2PC analytical capabilities should also include automated spectral flow-cytometry and imaging flow-cytometry capabilities to analyze cells.

• M2PC analytical capabilities should also include automated colony picking, Fluorescence-

Activated Cell Sorting (FACS), sequencing and quantitative PCR (a.k.a., qPCR) capabilities to analyze cells and to allow for high accuracy transcript quantification.

• M2PC analytical capabilities should also include automated plate readers which can address a wide range of scientific questions when paired with various dyes/probes/enzymes including

Optical Density, Live/Dead assays, Glucose/Sucrose assays, pH, Phosphate abundance, and

Protein binding assays.

APPENDIX B

Scheduling Software for the High Throughput Automated Phenotyping Platform (HTP-APP)

A critical functional requirement of the M2PC is the flow of data both into, within, and out of the M2PC.

The M2PC facility is envisioned to run a high mix of workflows across shared equipment. The system will need to be capable of dynamically rescheduling in response to new protocol run submissions, addition/removal of labware, and errors/slowdowns/accelerations resulting from physical execution of protocol runs. Because the system requires multiple instances of certain devices to accomplish the throughput necessary, it will need to be able to dynamically re-route samples to any instance of a given device based on availability at time of scheduling. In addition, the software will be required to support human interaction with storage devices during protocol run execution to allow for the manual addition or removal of labware. Further, the system shall be capable of running multiple protocol runs of different types simultaneously, interleaving protocol runs to maximize system throughput. It is envisioned that remote planning and operations will be part of the scheduling software.

Remote Planning and Operations:

The architecture of the system must allow for an exceptional degree of remote monitoring, operations, and troubleshooting. This confers advantages to a facility with a national or global user base whereby remote users may submit work, monitor progress, review data, and execute dynamic experimental changes. Real-time data allows researchers to adapt experiments and maximize their experimental output in direct collaboration with EMSL staff. Moreover, EMSL staff will have the ability to monitor and maintain the system while operating under a hybrid work model. Troubleshooting and system monitoring can occur while employees work from home or remotely. A key performance parameter is identified as a demonstration that remote users can run pre-defined EMSL protocols to be executed autonomously within M2PC across culturing, assaying, and analyses.

Laboratory Information Management System (LIMS):

To ensure successful operation of this capability at the EMSL user facility it is important to connect the data acquisition software to the EMSL Laboratory Information management System (LIMS) and downstream archival data management systems. EMSL leverages L7 Enterprise Science Platform (L7/ESP) as a Laboratory Information Management System (LIMS) that captures data from analytical instrumentation.

L7/ESP is a comprehensive software platform that optimizes laboratory workflows, sample tracking, and experimental data. It facilitates sample registration, tracking, and disposal, while automating tasks and coordinating workflows. L7/ESP integrates with instruments to capture and import data, enforces quality control measures, supports compliance, provides reporting and data analysis capabilities, and includes features for experiment design and electronic notebook functionality.

L7/ESP key capabilities are described below:

https://l7informatics.com/esp/

1. Experiment Design: L7/ESP incorporates experiment design capabilities, allowing researchers to plan and design their experiments within the system.

2. Electronic Notebook: L7/ESP includes an electronic laboratory notebook functionality, enabling researchers to document their experimental procedures, observations, and findings digitally.

3. Sample and Data Tracking: L7/ESP has the ability to track the entire lifecycle of a sample, from sample registration to disposal. This allows researchers to easily locate and retrieve samples, ensuring efficient laboratory operations.

4. Workflow Management: L7/ESP supports the management of the laboratory's workflow by automating and coordinating various tasks and track the progress of each sample through different stages of analysis, ensuring that all necessary steps are completed.

5. Instrument Integration: L7/ESP integrates with instruments, allowing direct data capture, and automatic importation of results.

6. Quality Control and Compliance: L7/ESP has the ability to enforce quality control measures by defining standard operating procedures and ensuring adherence to them.

L7/ESP is equipped with a wide range of pre-built connectors to lab instruments, data analysis and third-party software systems and logistics systems. The HTP-APP scheduling software will need to be able to take advantage of these prebuilt capabilities that can connect the LIMS to the scheduling software. HTP-

APP scheduling software vendor will work closely with the EMSL experts in LIMS to make these connections. The software vendor ensures smooth data flow between the systems to ensure data integrity and flow of information.

HTP-APP Scheduling Software Details:

The HTP-APP is expected to support or manage capture of instrument performance, sample ID, analytical results in real-time or near real-time, instrument calibration and quality control information, and associate these data with parallel data and metadata stored on EMSL’s LIMS system. The vendor software is expected to provide Application Programming Interface (API) to support communication with the

EMSL Software systems, and an SDK (Software Development Kit) to guide development of the needed communication layer between the vendor system and EMSL Software systems. The scheduling software must have the following requirements:

• 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 (L7/ESP)

Potential Option for a High-Level Architecture of the Scheduling Software:

The HTP-APP is expected to support or manage capture of instrument performance, sample ID, analytical results in real-time or near real-time, instrument calibration and quality control information, and associate these data with parallel data and metadata stored on EMSL’s LIMS system. The vendor software is expected to provide Application Programming Interface (API) to support communication with the

EMSL Software systems, and an SDK (Software Development Kit) to guide development of the needed communication layer between the vendor system and EMSL Software systems. The scheduling software must have the following requirements:

• 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 (L7/ESP)

Potential Option for a High-Level Architecture of the Scheduling Software:

A potential high level software architecture could have at least the following three components:

Design Engine – This feature would ingest experimental intention information and combine it with information in the LIMS. For example, if the experimental intention calls for performing an experiment on a certain microbial strain, the design engine would determine what primers in the system’s inventory would be needed to create that strain.

Workflow Engine – This feature would store workflow templates, which define the set of actions required to execute an entire biological workflow. It receives a series of inputs from the design engine that fully parameterize the workflow template and allows for each workflow step to be executed. While executing a parameterized workflow, the engine also makes decisions about how to proceed between workflow steps. Workflow steps could be gated by the completion of previous steps or could be gated on generated experimental data. Workflow parameters from either the design engine or provided by users would be captured and associated with experimental data.

Data Processing Engine - Data produced by the system would be ingested and contextualized before loading the results back into the LIMS. Information related to (i) system metadata which is the information related to the execution of protocol runs, (ii) device telemetry data which is a real-time data like temperature, pressure, etc., and (iii) experimental data which results of experimental measurements from an instrument that are performed during an experiment may be produced during the execution of protocol runs, and should be available for handling by a data processing engine. Raw instrument data should be ingested into EMSL Archive. Ensure data privacy and security at rest and transit.

In addition, the scheduling software would interact with the following upstream and downstream

Software components which are not provided by the vendor:

Laboratory Information Management System (LIMS) – This EMSL system (L7/ESP) stores, tracks, and relates all of the data associated with samples that are used in M2PC. Scheduling Software will provide the authentication and authorization or leverage existing EMSL authentication for a user to login through validating credentials to access the system. EMSL is also equipped with Aurora Archive to store the raw instrumentation data and Analysis Database where data analysis and results are saved. All of EMSL data can be accessed through EMSL Science Central Data Portal.

Experimental Intention Tools - Any software tools that a user may use to communicate their experimental intent. The output of these tools can be a series of experimental input factors that might tell the system. These tools would most likely manifest themselves as common statistical software that is capable of running a design of experiments.