Investigating Spaceflight Health Risks on the ISS (LSRS AO 2018)

Announcement of Opportunity

Publication date: February 14, 2018

Application deadline: April 26, 2018

1. Introduction

Future human exploration of space is expected to go beyond Low Earth Orbit (LEO) to targets such as near-Earth objects and Mars. The resulting expeditions will require extended periods of exposure to weightlessness and space radiation, with confinement and isolation in the extreme environment of space, all of which are linked to substantial health and performance risks.The Canadian Space Agency (CSA) is interested in human spaceflight and maintaining a healthy and highly qualified astronaut corps capable of participating in space exploration missions. To achieve this, the CSA's Health and Life Sciences (HLS) group conducts activities generating knowledge in fields that sustain human space flights, mitigate health risks and develop countermeasures for those missions.

Although the International Space Station (ISS) is equipped with health and life sciences research tools, existing instrumentation for the analysis of biological samples is sub-optimal compared to capabilities found in laboratories on Earth. Also, current physiological monitoring instruments available on ISS are not suited for continuous monitoring for prolonged period of time. Moreover, several of these devices are often required for more than one physiological parameter to be monitored. The current protocols are time-consuming, often limit crewmember mobility, and involve complicated and complex data management. To address these limitations, the CSA has commissioned two Life Science Research Systems (LSRS). They are novel bio-analyzer (Bio-A) and bio-monitor (Bio-M) systems to investigate the risks of human flights. These systems will be deployed aboard the ISS in support of scientific experiments.

Bio-A: The Bio-A System can perform on-orbit bodily fluids testing with soluble biomarkers analysis and cellular labelling. The system is capable of analyzing whole blood, plasma, saliva, and urine. Both assays can be performed from a single 50-150 microliters sample with each analysis carried out in parallel or independently. The soluble biomarker microchips can quantify up to five soluble protein biomarkers simultaneously from a single 60 microliter whole blood sample, whereas the cellular labelling and assessment will enable morphological cytometry as well as immunophenotyping for the quantification of white blood cells and the classification of at least three subpopulations from a 30 microliter whole blood sample. All microchips and reagents will be provided by the CSA and are single use reagents. Technical details are described in Appendix A (Bio-A).

Bio-M: The Bio-M System can monitor key physiological parameters of crewmembers' health state over a long period of time before, during and after space missions. The Bio-M System is based around sensors that do not interfere with the crewmember's daily activity. It is designed to record vital signs, sleep quality and activity level using a wearable "smart" garment fitted with various non-invasive physiological sensors. The recorded parameters are of a quality comparable to current technologies used for clinical and research purposes on the ground and sufficient to meet research criteria. The Bio-M System can continuously monitor: Cardiovascular (Electrocardiogram (ECG); Heart Rate (HR); Systolic Blood Pressure (BP); Peripheral Blood Oxygen Saturation (SpO2), Respiration Rate (RR); breath Tidal Volume (VT); Minute Ventilation (VE), Activity (crewmember's full-body orthogonal triaxial acceleration; actigraphy; cadence; and step-to-step step count), and Skin Temperature (forehead or torso). Technical details are described in Appendix A (Bio-M).

The aim of the present Announcement of Opportunity (AO) is to solicit scientific protocols that will be used to investigate health risks associated with space travel and make optimal use of the Bio-A or Bio-M systems. Since crew time, stowage and cold stowage as well as launch mass allocations are very limited, the proposed experiments must minimize resource requirements such as crew time, hardware transfer to the ISS or cold stowage. Operation and experimentation procedures must be simplified accordingly.

This AO is consistent with the terms and conditions of the CSA Class Grant and Contribution Program to Support Research, Awareness and Learning in Space Science and Technology – Research Component.

Applicants are asked to read the following AO thoroughly before submitting their applications. This AO was prepared to help applicants complete the application process, and outlines key elements, including mandatory criteria for eligibility, details on eligible projects and the selection process. In the event of any discrepancies between this AO and the individual funding agreements governing a project, the latter document(s) will take precedence.

2. AO Objectives

Through this AO, the CSA is seeking to financially support Canadian researchers who will design and implement scientific protocols to investigate health risks associated with space travel.

More specifically, the proposal(s) selected through this CSA competition will maximize the use of Bio-A and Bio-M systems for in situ data collection to:

• Contribute to the understanding, mitigation or elimination of health risks associated with human space flight;
• Contribute to a better understanding of similar health issues or applications on Earth;
• Propose innovative space life science studies to be conducted on the ISS including those that may use astronauts as subjects;
• Minimize requirements for transport of materials to and from the ISS;
• Foster training of highly qualified personnel in space health and life sciences.

3. Eligibility Criteria

3.1 Eligible Recipients

Eligible recipients (beneficiaries) for contributions are:

• Canadian universities;
• Not-for-profit organizations established and operating in Canada (performing research).

3.2 Eligible Projects

Projects eligible for funding under this AO are those wherein eligible recipients submit projects for which:

1. Canadian researchers are Principal Investigator (PI) in new research projects, or
2. Canadian researchers are PI of the proposed research project, and it is a contribution to an international project already selected by another space agency.

There is no limit on the number of proposals presented per investigator. An investigator can be a PI in one project submitted in response to this call and a Co-Investigator (Co-I) on other proposals.

Projects falling within CSA priorities and in the second category (participation in international projects) can be submitted if they demonstrate how the proposal will enhance the value of the international project. A letter of support from the international PI will be required.

Eligible research projects are innovative space life science studies to be conducted on the ISS using either the Bio-A and Bio-M systems (or both) for in situ data collection. Applicants will have to associate the project with one of the LSRS system. If both technologies are required, the project will be associated with the technology essential for the main objectives, along with a justification in the project description.

Research projects already presented through the recent NASA NRA will not be funded through this AO, unless it is demonstrated that the LSRS strongly increase the scientific impact of the project. The CSA will then fund the project submitted to and selected through this AO.

All development phases necessary for a project are eligible. Any logical breakdown or combination of these phases can constitute a funded project. However, breaking down a project into numerous phases to obtain more than the maximum grant or contribution is not allowed. Furthermore, even if the maximum funding for one project is not reached, the completion of a funded phase does not automatically guarantee funding of the remaining phases. Details of eligible costs of the projects financed under this AO are listed in Section 6.2.

Projects requiring the collection of samples from animals or plants are not eligible under this announcement due to on-board resource limitations and will not be considered. However, projects proposing the analysis of samples from either a human source, or from on-board cell culture facilities will be considered for funding.

Proposals requiring the development of new hardware or software are not eligible under this AO and will not be considered.

Guidelines on ISS investigations using the LSRS are presented in Appendix B.

A suggested structure for the detailed project description is included in Appendix C.

3.3 Alignment with CSA priorities

To be eligible, projects supported under this AO must be aligned with CSA priority outcomes, as stated in the 2017-2018 Departmental Plan.^{Footnote 1} At the highest level, the contribution of Space Exploration "fosters the generation of knowledge as well as technological spin-offs that contribute to a higher quality of life for Canadians." Consideration will be given to activities that are aligned with the mandate to "identify, understand, mitigate or eliminate health risks associated with human space flights, and to understand and address the needs of humans during those missions." The most important health risks associated with human space flights (i.e. future long-duration human spaceflight missions) have been identified and are listed in Table 1.

3.4 Links to the Class Grants and Contributions Program Objectives

To be eligible, projects supported under this AO must contribute to the achievement of at least one of the following objectives:

• To support the development of science and technology relevant to the priorities of the CSA;
• To foster the continuing development of a critical mass of researchers and highly qualified people in Canada in areas relevant to the priorities of the CSA;
• To support information gathering, studies and research related to space.

4. Applications

4.1 Required Documentation

Applicants are required to submit a full proposal prepared in French or in English, which will include:

• A completed original application form signed by the duly authorized representative and the PI of the proposed project as stipulated in section 3.2;
• Two paper copies of the full proposal;
• A copy of the document(s) confirming the legal name of the applicant (must be confirmed by the organization's Office of Research);
• A copy of the application form (identical to the signed paper copy) and the detailed project, in a standard electronic media format (USB flash drive, CD or DVD). If there is any discrepancy between the hard and the soft copies, the hard copy takes precedence;
• Letters from other funding contributors confirming their contributions, if applicable;
• For Canadian projects associated with an international study, a letter from the international PI is required, confirming that the proposed research will enhance the study.
• Declaration on Confidentiality, Access to Information Act and Privacy Act form signed by the duly authorized representative (refer to the Applicant Declaration on Confidentiality, Access to Information Act and Privacy Act section included in the application form); and
• For organizations in Quebec, M-30 Supporting Documentation form completed and signed by the duly authorized representative (refer to the M-30 form for organizations in Quebec included in the application form).

It is the applicant's responsibility to ensure that the application complies with all relevant Canadian legislation and bylaws (federal, provincial/territorial and municipal).

Before the investigation transitions to the operation phase, recipients will be required to submit to the CSA evidence of approval from institutional and space agency research ethics boards, if relevant.

Applications must be mailed to the CSA at the following address:

Important information:

• Proposals must be received at the CSA no later than April 26, 2018 at 2 p.m. (EST).
• Applications sent by email will not be accepted.
• Incomplete applications shall not be considered.

Questions and answers related to this AO will be posted on the CSA website in the Frequently Asked Questions (see Section 9).

4.2 Service Standards

Applicants will be notified in writing of decisions regarding their application. Selected applications will be announced on the CSA website. The CSA has set the following service standards for processing times, acknowledgement of receipt, funding decisions and payment procedures.

Acknowledgement: The CSA's goal is to acknowledge receipt of proposals within 2 weeks of receiving the completed application package.

Decision: The CSA's goal is to respond to the proposal within 20 weeks of the AO's closing date and to send a contribution agreement for signature within 16 weeks after formal approval of the proposal.

Payment: The CSA's goal is to issue payment within 6 weeks of the successful fulfillment of the requirements outlined in the contribution agreement.

Compliance with these service standards is a shared responsibility. Applicants must submit all required documentation in a timely fashion. Service standards may vary by AO.

5. Evaluation

5.1 Evaluation Process

Applications will first be evaluated for eligibility. Only applications that have passed the eligibility assessment described in (Section 5.2) will be given further consideration.

Once the eligibility is confirmed, full proposals will then undergo an evaluation (covering criteria such as benefits to Canada, project feasibility, resources, results and impacts as well as risk and risk mitigation measures). This will take the form of a scientific merit review based on the peer-review criteria (Section 5.3). The scientific merit review will be conducted by a panel of international scientific or technical experts. The number and diversity of experts required will be determined by the response to this research announcement and by the variety of disciplines represented in the proposals. The scientific merit review panel will assign a score from 0 to 100 or a designation of "not recommended for further consideration" based upon the intrinsic scientific merit of the proposal. Before a final decision is made, the CSA's Program Manager responsible for this AO may seek input and advice from other organizations, including (but not limited to) federal, provincial, territorial and municipal government agencies and organizations. This score will reflect the consensus of the panel. Proposals that receive a score in the scientific merit review that is lower than 70/100 will not be further evaluated.

Proposals with a successful scientific review will then undergo a flight feasibility review as described in Section 5.4 to determine if their implementation on the ISS is possible. A team of CSA engineers and scientists experienced in the development, integration and operation of space flight experiments will conduct this review. For this reason, experimental requirements and procedures should be clearly and succinctly explained in terms that a layperson can understand. This flight feasibility review will result in a score from 0 to 100 for each proposal that will identify each proposal as "low risk," "medium risk," or "high risk." The main elements of the flight feasibility review are:

• Functional Requirements
• Operational Feasibility
• Environmental Health and Safety

The final score for each proposal will be based on the score for science merit (75%) and for feasibility (25%). Successful proposals will be separated in two ranking lists, one for Bio-A and one for Bio-M, based on the final score of each proposal and the technology identified in the Application Form. The first proposal of each list will be funded, then the second, and so on. The number of projects funded under this AO will depend on funding and resource availability.

5.2 Eligibility Criteria

• Represents an eligible recipient as defined in Section 3.1;
• Represents an eligible project as defined in Sections 3.2, 3.3 and 3.4;
• Meets program funding provisions in Section 6.1.

5.3 Scientific Merit Criteria

The following language ladder is provided as a guide for evaluation and includes examples of justification for each score.

Passing proposals must receive at least a minimal score for each criterion and also obtain a total score of at least 70, which is higher than the sum of all the minimal scores.

Science quality

- Originality

Description: This criterion evaluates whether the proposal addresses a significant gap in health research related to spaceflight. The originality of the proposed research in terms of the hypotheses/research questions addressed and novelty enabled by the LSRS technology will be assessed.

Scoring:

• Maximum: 16
• Minimum: 9

D: The hypotheses and research questions have been explored before. The proposed applications of the LRSR technology will not result in significant new knowledge generation.

C: The hypothesis/research questions contain limited original elements and represent incremental research. The proposed use of the LSRS technology does not take advantage of the full capabilities of the LSRS technology.

B: The hypothesis/research questions are original and represent a new approach. The project is likely to result in significant scientific advances. The proposed use of the LSRS technology enables a novel approach to study health risks of spaceflight.

A: The hypotheses/research questions are built on ground research, but have not been investigated before in space. The project is likely to result in scientific breakthrough. The proposed use of the LSRS technology is highly innovative and will enable new types of experiments on the ISS.

- Impact on health risk understanding and mitigation

Description: This criterion evaluates the potential of the proposal to decrease one or more risks of human spaceflight if the objectives are met. Potential to increase our understanding of the risks associated with human spaceflights or to propose mitigation strategies will be evaluated. This criterion mainly addresses the expected outcome of the proposed research in the context of risk understanding and mitigation.

Scoring:

• Maximum: 16
• Minimum: 9

D: The study is unlikely to increase our understanding of the risks of human spaceflight or provide any mitigation strategy.

C: The study will only marginally increase our understanding of the risks of human spaceflight and provide only minor insights into mitigation strategies.

B: The study is likely to increase our understanding of the risks of human spaceflight and lead to substantial insights into provide a mitigation strategies.

A: The study is very likely to provide a critical increase of our understanding of the risks of human spaceflight and/or a credible, novel mitigation strategy for one or more specific health risks of human spaceflight. The knowledge is likely to contribute to the development of new countermeasures.

Research approach

- Validity of the research approach

Description: This criterion evaluates how the research approach builds upon a successful foundation of ground or previous flight studies. It evaluates the completeness of the literature review and its relevance to the study design/research plan.

Scoring:

• Maximum: 12
• Minimum: 7

D: The research approach is not based upon a successful foundation of ground or previous flight studies. The literature review is missing or inadequate/incomplete.

C: The research approach is indirectly related to successful ground or previous flight studies. The literature review is missing or inadequate/incomplete.

B: The research approach is based in part upon a successful foundation of ground or previous flight studies. The literature review contains some relevant references but some important documents are missing.

A: The research approach is largely based upon a successful foundation of ground or previous flight studies. The literature review is exhaustive and covers all aspects of the proposed study.

- Methodology

Description: This criterion evaluates the appropriateness of the proposed research design, research methods and feasibility of the research approach to achieve the objectives.

Scoring:

• Maximum: 16
• Minimum: 9

D: The proposed methodology is unlikely to support the objectives of the study or is poorly described. The research design lacks important details and the selected approach is not appropriate.

C: The proposed methodology may support the study's objectives. However there is a significant lack of details or it is poorly described. There may be better approaches to achieve the objectives.

B: The proposed methodology is likely to achieve the objectives and well described. However, some aspects of the methodology are not appropriate or well described.

A: The proposed methodology is excellent and clearly described, giving a high level of confidence that the objectives will be achieved.

- Potential pitfalls

Description: This criterion evaluates how the proposal addresses project risks and whether it includes mitigation strategies.

Scoring:

• Maximum: 8
• Minimum: 5

D: The proposal fails to identify and address potential pitfalls and does not include a risk mitigation strategy.

C: The proposal identifies some of the potential pitfalls of the project but proposes inadequate mitigation strategies.

B: The proposal identifies the major potential pitfalls and proposes an adequate mitigation strategy.

A: The proposal clearly identifies all potential pitfalls and proposes an excellent mitigation strategy.

Research team

- Research team expertise and complementarity

Description: This criterion evaluates the availability of all the required expertise in the team in order to successfully accomplish the proposed work. Specific aspects of the evaluation include qualifications of the applicant(s) and appropriateness of the team to carry out the proposed research, in terms of complementarity of expertise.

Scoring:

• Maximum: 8
• Minimum: 5

D: The proposed team does not have the required expertise or the proposal does not address this criterion.

C: The team has deficiencies in the completeness of the skills of its members, is lacking important expertise in field of research relevant to the study. The proposal suggests that the team may not be capable of achieving the objectives of the project.

B: The proposal demonstrates that the team has most of the expertise required to achieve the objectives of the study, however some minor expertise may be lacking or complementarity of the expertise is not optimal.

A: The completeness of the team is very well demonstrated through the complementarities of skills of its members and by the roles/tasks that they are assigned during the study. The expertise of the proposed team demonstrates that it is highly capable of achieving the objectives.

- Research team experience and productivity

Description: This criterion evaluates the experience of the team in the proposed area of research as demonstrated by scientific productivity over the past five years and past achievements in the proposed field of research and methodology.

Scoring:

• Maximum: 8
• Minimum: 5

D: The team's scientific productivity in this field of research is poor and the experience in similar research studies is not sufficient.

C: Although the team includes experts in the field of research, some members of the team have limited experience or the overall productivity of the team is less than average. Experience of the team in the proposed area of research or with the proposed methodology is not clearly demonstrated.

B: The team includes established members with good publication productivity in their field and some experience in similar studies.

A: The team is composed of experts in the proposed field of research, with a high productivity in their field. It is clear that the team has successfully conducted studies of similar scope.

- Training Plan

Description: This criterion evaluates the training plan included in the proposal and the potential of the project to support training of students.

Scoring:

• Maximum: 8
• Minimum: 5

D: The proposal does not include a training plan or the supporting information provided misses all the key information and details.

C: The proposal includes a training plan, however it provides an average assessment with little supporting information about how the project is expected to impact on the training of students.

B: The diversity of experience, knowledge and professional skills that each student will receive are provided but minor details are missing.

A: The experience, knowledge and professional skills that each student will receive is provided. The proposal provides a complete assessment with all supporting information about how the project is expected to impact on the student in their higher education or future career.

In situ data analysis

Description: The benefit of having in situ, almost real-time or continuous data collection to achieve the objectives will be assessed. The impact of on-board data collection and why it is important for the project will be evaluated. This criterion also evaluates the need for LSRS technologies to achieve the objectives and the value of alternative modes of data collection.

Scoring:

• Maximum: 16
• Minimum: 9

D: The proposal fails to demonstrate that the science objectives require in situ or continuous data collection or the proposal does not provide a justification for the benefits of LSRS for the project.

C: The proposal includes a justification for in situ or continuous data collection; however the presence of on-board LSRS instruments constitutes a minor benefit to achieve the science objectives. Alternatives for data collection exist and the project will only slightly benefit from the presence of on-board instrumentation.

B: The proposal demonstrates a strong justification for in situ or continuous data analysis and the science objectives were determined in consideration of the on-board data collection system. It is clear that alternatives for data collection are difficult or impossible to implement.

A: It is convincingly demonstrated that the presence of on-board data collection instruments is essential to achieve the objectives of the study. The proposed project is clearly made possible because of the presence of the LSRS on-board the ISS. There is no alternative for data collection in the context of the proposed project objectives.

5.4 Feasibility Assessment Criteria

The Flight Feasibility Review will be conducted for each flight experiment proposal that receives a scientific merit score greater than 70%. A team of engineers and scientists experienced in the development, integration and operation of space flight experiments will conduct this review, using criteria included in Table 4 and described below.

Description of feasibility criteria:

1-In-flight crew time per subject

Description: Crew time available on-board the ISS for Canadian investigations is limited. This criterion evaluates how much in-flight crew time is required per subject for the investigation.

Scoring:

• Maximum: 20
• Minimum: 0

D: Total in-flight crew time required per subject is more than 5 hours.

C: Total in-flight crew time required per subject is between 2 and 5 hours.

B: Total in-flight crew time required per subject is between 1 and 2 hours.

A: Total in-flight crew time required per subject is less than 1 hour.

2-Sample size (n)

Description: ISS crew size limits the number of available subjects for human research. This criterion evaluates the impact of the number of subjects to be recruited over 5 years on experiment feasibility.

Scoring:

• Maximum: 10
• Minimum: 5

D: Proposed subject number is more than 20 subjects.

C: Proposed subject number is between 20 and 15 subjects.

B: Proposed subject number is between 14 and 10 subjects.

A: Proposed subject number is less than 10 subjects.

3-Window of in-flight sessions

Description: The in-flight windows could fall inside critically limited crew access periods. There are two such limited crew access periods: 1st two weeks on orbit (Launch+0d to Launch+15d) and 1 week before return (Return-7d to Return-0d). This criterion evaluates the requirement to perform in-flight sessions during these periods.

Scoring:

• Maximum: 5
• Minimum: 0

D: The experiment proposes more than two activities during a limited crew access period.

C: The experiment proposes two activities during a limited crew access period.

B: The experiment proposes one activity during a limited crew access period.

A: The experiment proposes no activity during a limited crew access period.

4-Windows of pre- and post-flight sessions

Description: The pre- and post-flight windows could fall inside critically limited crew access periods. There are two such limited crew access periods: Launch-60d to Launch-0d and Return+0d to Return-7d. This criterion evaluates the requirement to perform pre- or post-flight sessions during these periods.

Scoring:

• Maximum: 5
• Minimum: 0

D: The experiment proposes more than two activities during a limited crew access period.

C: The experiment proposes two activities during a limited crew access period.

B: The experiment proposes one activity during a limited crew access period.

A: The experiment proposes no activities during a limited crew access period.

5-New assay development

Description: The LSRS rely on pre-defined assays to collect science data (microchips and cellular labeling for Bio-A; temperature, activity, BP, etc.) for Bio-M). This criterion evaluates how many new assays (new microchips, cellular labeling assays, or others) will be required for the project. More information on available assays can be found in Appendix A.

Scoring:

• Maximum: 20
• Minimum: 5

D: The experiment requires the development of more than 6 new assays.

C: The experiment requires the development of 4 to 6 new assays.

B: The experiment requires the development of 1 to 3 new assays.

A: The experiment does not require the development of new assays and only relies on assays already available.

6- Transportation to and from orbit

Description: Feasibility of an ISS investigation is affected by the resources required to launch equipment or samples in orbit and to return them to the ground. This criterion evaluates the launch or return requirements for the project.

Scoring:

• Maximum: 10
• Minimum: 0

D: The experiment requires the launch or return of more than 2 kg of sample or equipment per subject.

C: The experiment requires the launch or return of 1 to 2 kg of sample or equipment per subject.

B: The experiment requires the launch or return of less than 1 kg of sample or equipment per subject.

A: The experiment does not require sample or equipment transportation.

7- Conditioned stowage

Description: Cost and complexity of an experiment are affected by the necessity for conditioned (cold) stowage on the ground, during launch and return, or on-board the ISS. This criterion evaluates whether conditioned stowage is required for the project.

Scoring:

• Maximum: 20
• Minimum: 0

D: The experiment requires conditioned stowage on the ground, on-board the ISS and during launch or return of samples or equipment.

C: The experiment requires conditioned stowage on the ground and on-board the ISS.

B: The experiment requires conditioned stowage only on the ground.

A: The experiment does not require conditioned stowage.

8- Shelf-life of consumables

Description: Shelf-life of consumables at ambient temperature affects planning and implementation of the investigation, by adding the requirement for frequent launches for resupply or the necessity to keep consumables in conditioned stowage. This criterion evaluates the impact of shelf-life consumables (other than the ones provided by CSA) on the feasibility of the project.

Scoring:

• Maximum: 10
• Minimum: 0

D: Consumables can be stored less than 3 months at ambient temperature.

C: Consumables can be stored between 3 and 6 months at ambient temperature.

B: Consumables can be stored between 6 months and 1 year at ambient temperature.

A: Only consumables provided by CSA are required.

6. Funding

6.1 Available Funding and Duration

The total maximum funding amount given in contribution for each project will be $750,000 for new Canadian projects and $500,000 for Canadian participation in International projects, over a maximum period of 5 years.

The number of projects funded under this AO will depend on funding availability.

The CSA reserves the right to reject any proposals or reduce the amount of the contributions at its entire discretion.
Approved proposals will be eligible for a total amount of Canadian government assistance (federal, provincial, territorial and municipal) of up to 100% of total project costs.

To determine the amount of funding to be allocated, consideration will be given to the availability of CSA funds, the total cost of the project, and the other confirmed sources of funds provided by other stakeholders and the applicant.

Applicants must identify all sources of funding in their applications and confirm this information in a funding agreement if the project is selected for funding. Upon completion of a project, the recipient must also disclose all sources of funding.

6.2 Eligible Costs

Eligible costs are direct expenses associated with the delivery of the approved project and that are required to achieve the expected results of the project.

For this AO, recipients will not be responsible for costs of integration, launch, and operation of their study on the ISS; however, the recipients will be responsible for supplying extensive documentation to support the development, integration, and operation of their study. Typically, a minimum of 0.5 Full Time Equivalent is required for this.

The cost of manufacturing and launching Bio-A and Bio-M consumables will not be charged to the investigator and should not be included in the proposed budget.

Please note that your proposal to this CSA AO cannot include as eligible costs any costs related to non-Canadian-based Co-Is or non-Canadian-based PIs or their work within the proposal. These costs should be submitted to the appropriate national agency for funding.

Expenses will be covered subject to the applicant signing a funding agreement, in the form of a contribution, with the CSA.

The eligible costs for contributions under this AO are the following:

• Access fees;
• Accommodation and meals allowances;
• Acquisition, development and printing of materials;
• Acquisition or rental of equipment;
• Consultant services;
• Data acquisition;
• Data management;
• Laboratory analysis services;
• Licenses and permits fees;
• Material and supplies;
• Overhead (administrative) costs (not to exceed 20% of eligible costs for Canadian universities and 15% for other eligible recipients);
• Participation fees at conferences, committees and events;
• PST, HST and GST net of any rebate to which the recipient is entitled to and the reimbursement of any taxes for goods and services acquired in a foreign country net of any rebate or reimbursement received in the foreign country;
• Publication and communication services;
• Salaries and benefits;
• Translation services; and
• Travel.

7. Funding Agreements

7.1 Payments

The CSA and each of the successful applicants (the recipients) will sign a funding agreement which is a condition for any payment made by the CSA with respect to the approved project.

Payments for contribution agreements will be made in accordance with the process and the reporting requirements described in the signed funding agreement. Upon notice of a successful application, the CSA will have no liability until a funding agreement is signed by both parties. Only eligible costs incurred after the funding agreement is signed and indicated in the agreement will be reimbursed.

Contribution agreements will have the following structure:

1. Year 1: Development of requirements. A comprehensive science requirement assessment will be done, during the first year of the project, by the CSA and possibly, if deemed useful by the CSA, such review may involve ISS partners. At the conclusion of Year 1, the CSA will make a decision on proceeding to Years 2 to 5. The CSA may decide to stop the project at this stage, for reasons of feasibility, lack of resources, or for example lack of Co-Is funding by an international partner, or changes in programmatic direction. The CSA may also decide to limit subsequent funding to a shorter operational period.
2. Years 2 to 5: Integration and Operations. During years 2 to 5 the CSA will integrate the activity into ISS planning, and then operate the study on the ISS.

7.2 Audit

The recipient of a funding agreement shall keep proper records of all documentation related to the funded project, for the duration of the project and for six (6) years after the completion date of the project, in the event of an audit. This documentation shall be available upon request.

7.3 Conflict of Interest

In the funding agreement, the recipient will certify that any former public office holder or public servant it employs complies with the provisions of the relevant Conflict of Interest and Post-Employment Code for Former Public Office Holders and the Values and Ethics Code for the Public Sector respectively.

7.4 Intellectual Property

All intellectual property developed by the recipient in the course of the project shall vest in the recipient.

7.5 Organizations in Quebec

An organization in Quebec whose operations are partially or fully funded by the province of Quebec may be subject to the Act Respecting the Ministère du Conseil exécutif, L.R.Q., Chapter M-30.

Under Sections 3.11 and 3.12 of this Act, certain entities/organizations, as defined in this Act, such as municipal bodies, school bodies, or public agencies, must obtain an authorization by the Secrétariat du Québec aux affaires canadiennes (SQRC), as indicated by the Act, before signing any funding agreement with the Government of Canada, its departments or agencies, or a federal public agency.

Consequently, any entity that is subject to this Act is responsible for obtaining such authorization before signing any funding agreement with the Government of Canada.

Quebec applicants must complete, sign and include the M-30 Supporting Documentation Form with their application.

7.6 Performance Measurement

The CSA will ask the recipients to report on an annual basis on certain aspects of their projects such as:

• Knowledge Creation
  • Knowledge production (including publications)
  • Presentations
  • Intellectual property (including patents)
• Capacity Building
  • Project's research team (including highly qualified personnel supported)
• Collaboration
  • Partners' contributions
  • Partnerships
  • Multidisciplinarity

As a courtesy, the CSA would like to receive a copy of publications arising from the work, and to be informed in advance of significant press releases or media interest resulting from the work.

8. Privacy Notice Statement

The CSA will comply with the federal Access to Information Act and Privacy Act with respect to applications received. By submitting personal information, an applicant is consenting to the collection, use and disclosure of that information in accordance with the following Privacy Notice Statement which explains how the applicant's information will be managed.

Necessary measures have been taken to protect the confidentiality of the information provided by the applicant. This information is collected under the authority of the CSA Class Grant and Contribution Program to support the Research, Awareness and Learning in Space Science and Technology – Research Component, and will be used for the evaluation and selection of proposals. Personal information (such as contact information, biographical information, etc.) included in the rejected proposals will be stored in a CSA Personal Information CSA Bank for five (5) years and then destroyed (Personal Information File no. ASC PPU045). Personal information included in the successful proposals will be kept along with the proposal results for historical purposes. These data are protected under the Privacy Act. According to the Privacy Act, the data linked to an individual and included in the proposal being evaluated can be accessed by the specific concerned individual who has rights with respect to this information. This individual may, upon request,

1. be given access to his/her data and
2. have incorrect information corrected or have a notation attached.

Applicants shall note that for all agreements over $25,000, information related to the funding agreement (amount, grant or contribution, name of the recipient and project location) will be made available to the public on the CSA website. For additional information on privacy matters prior to submitting a proposal, please contact:

9. Frequently Asked Questions (FAQ)

It is the responsibility of the applicants to obtain clarification of the requirements contained herein, if necessary, before submitting an application.

For any questions related to the AO, applicants shall use the following generic email address lecedessetc-thegandccoe@asc-csa.gc.ca. Questions and answers related to this AO will be posted on the CSA website in the Frequently Asked Questions section of this AO. The CSA will respond to questions received before April 12, 2018 at 4 p.m. (EST).

Within two weeks after posting the AO, the CSA will hold a bilingual webinar to inform the Life Science community about this opportunity and answer questions related to the announcement. Registration to this webinar held through WebEx is free and mandatory. If you are interested in attending this online event, please send an email with your name, email address, institution, position and area of research, to the following address: santespatiale-spacehealth@asc-csa.gc.ca. Connection information (internet and telephone) will be provided to you by email.

At any point, applicants are welcome to share with the CSA their comments or suggestions regarding the AO, the program or the process. Applicants may either use the generic email address or the generic web-based Comments and Suggestions Box.

Appendix A: Bio-A and Bio-M Technical Details

Bio-analyzer System (Bio-A)

The instrument characteristics presented in this appendix are accurate at the time of publishing this AO. Since the proposed system is not finalized yet, some minor changes might be made to the technical specifications presented here. These changes, if any, should not affect the intended use or performance of the Bio-A System.

Definitions: Raw samples are the original liquid input samples; processed samples are raw samples that have gone through sample preparation and are ready to be analyzed; analyzed samples have gone through the whole Bio-A System and have provided data on cell population parameters or on concentrations of soluble biomolecules.

General performance

1. The Bio-A System can perform the analysis from raw blood samples collected following a finger prick (50-150 µl). Venous blood samples may also be acceptable if crew time is available.
2. The Bio-A System could also perform the analysis from other liquid sample types (for instance: plasma, saliva, urine, or cell culture media).
3. The Bio-A System can perform the two following assays:
   1. Soluble biomarker assessment: Quantify the concentration of up to ten soluble protein biomarkers simultaneously in a single liquid sample.
   2. Cellular labelling and assessment: Enable protein biomarkers quantification on the surface of cells (immunophenotyping) and perform cell counting.

Soluble Biomarker Assessment

1. The Bio-A microfluidic system (microchips) can measure soluble biomarker concentrations in the 100 to 5000 pg/ml range. Biomarkers with blood concentrations outside this range may be measurable, however this remains to be confirmed by testing.
2. Performance of the Bio-A System is comparable with the performance of an ELISA assay with less than 5% difference in the determination of biomarker concentrations.
3. The intra-assay coefficient of variation is inferior to 10% for the specified concentration range as determined by five repeated measurements using the same sample.
4. The inter-assay coefficient of variation is inferior to 15% for the specified concentration range as determined by five independent assays with the same sample.
5. Up to 10 biomarkers per blood sample will be quantified using two biomarkers microchips customized to quantify 5 biomarkers each. It may be possible to quantify more biomarkers using more microchips, however there may be limitations due to ISS resource constraints such as crew time. Applicants are encouraged to propose the assessment of more than 10 biomarkers, but some of them may be screened out based on technical or resource constraints.

During the development of this technology, antibodies against specific biomarkers were successfully tested. Examples of biomarkers detectable using the Bio-A (if the biomarker concentration is in the range mentioned above) includes: BDNF, Angiopoietin-2, beta-NGF, CA15-3, CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CEA, CRP, dP-EGFR, EGF, EGF-R, Endoglin, FAS, FAS-Ligand, FGF, G-CSF, GFP, GM-CSF, GRO-alpha, HER2, IFN-gamma, IGFBP-7 mono, IGFBP-7 poly, IL-1beta, IL-10, IL-12, IL-15, IL-18, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, Leptin, M-CSF, MIG, MMP-3, MMP-9, NCAM-1, NT-3, Osteopontin, PDGF-BB, P-EGFR, PSA, RBP4, SPARC, TNFalpha, TNFRI/p55, TNFRII/p75, uPA, uPAR(CD87), and VEGF.

While these are only examples, any biomarker detectable with an ELISA assay may be included in the proposal. Up to ten biomarkers for which commercial antibodies are available will be accepted in the list of biomarkers. Investigators are encouraged to propose the detection of other biomarkers, whether a commercial assay exists or not, however the CSA will determine over the development of the study whether they can be assessed.

Cellular Labelling and Assessment

1. The lens-less microscopy-based Bio-A System can support immunophenotyping and cell counting from blood or other sample types.
2. Cell identification and counting is performed following staining with specific dyes and exposure to antibody-coupled beads.
3. The cell count accuracy is equal to that of a commercial system (such as the Accuri C6 from Becton Dickinson) within 10% difference on monocytes, lymphocytes and granulocytes numbers, based on the analysis of 10,000 cells in flow cytometry.
4. The Bio-A System will demonstrate this level of cell counting accuracy (see (b) above) for five consecutive analyses of the same sample.
5. The Bio-A System will quantify at least three blood sub-populations from the same blood sample, if the cellular frequency is appropriate. As an example, the following cell populations from a single blood sample can be counted using a single assay:
   1. All white blood cells (CD45)
   2. CD4 Helper T lymphocytes
   3. CD8 Cytotoxic T lymphocytes

In general, cell-surface markers that are used in conventional flow cytometry can be used with the Bio-A system to measure the frequency of specific cellular phenotypes.

Additional cellular analyses could be done beyond those specified above and investigators are encouraged to include them in a list of supplementary measurements in the proposal. Depending on the frequency of these blood components, it may be possible to identify and count the following cell types in blood with performance comparable to gold-standard instrumentation:

• Erythrocytes
• Platelets
• Total Granulocytes
• Immature granulocytes
• Neutrophils
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils
• Reticulocytes
• Nucleated red blood cells
• Subtypes of leukocytes characterized on the basis of expression of cell surface antigens (e.g., CD3, CD4, CD8, CD14, CD19, etc.) both individually and in various simultaneous triplex and possibly higher order combinations.

The system could also carry out time lapse video microscopy, following any cell type over extended periods (e.g., to determine motility, growth, proliferation, viability, response to various stimuli, etc. etc.). The technology is able to detect and analyze any particle (living or inanimate) at the micron scale (e.g., for water quality testing). The technology could also be used as a biodosimeter (measuring the dosage of radiation exposure to an individual) on the basis of hematological measures (lymphocyte depletion kinetics, lymphocyte-neutrophil ratio, micronucleated reticulocyte count) coupled with already established radiation exposure estimating algorithms.

Bio-Monitor System (Bio-M)

The instrument characteristics presented in this appendix are accurate at the time of publishing this AO. Since the proposed system is not finalized yet, some minor changes might be made to the technical specifications presented here. These changes, if any, should not affect the intended use or performances of the Bio-M System.

In order to allow for real-time monitoring of the measured physiological parameters, the subjects will be able to sporadically use the graphical display of a dedicated application loaded on their iPad. It will also be possible to upload activity prescriptions with pre-set thresholds (maximum, minimum) associated with specified parameters. The display refresh-rate of the parameters is 1 Hz.

While this is not part of the evaluation process of this AO, applicants are encouraged to submit additional measurements (sensors) that the Bio-M should perform. The provided information will be used as part of our continuing improvement program and might lead to an improved version of the system for future users.

Physiological Data

General

1. The Bio-M System can perform continuous monitoring and recording of crew physiological parameters for up to 48 h.
2. The Bio-M System is non-invasive.
3. The Bio-M System measurements can be performed in a non-disruptive manner, not or only minimally interfering with crewmember daily living and working routine (e.g., no inflatable system operating on and off).

Cardiovascular

1. The Bio-M System can generate an ECG measure.
   1. The Bio-M System can provide an ECG measured with a sampling rate of 256 Hz.
   2. The ECG produced by the Bio-M System had its functional performance established through a validation in a laboratory context and compared to a recognized accepted standard. The performance level from this validation is expected to be comparable with that of an ECG captured by an ambulatory Holter-type monitor (recent Holter type device no older than 2 years, currently approved for medical use in Canada).
   3. The ECG has a resolution of 10 µV or better.
   4. In measuring the ECG, the Bio-M System common mode rejection ratio (CMRR) is at least 60 db.
   5. QRS^{Footnote 2} detection sensitivity and precision has at least a 99% score in low noise^{Footnote 3} situations (e.g.: at rest with no movement) and at least 95% in noisy situations (e.g. exercise such as jogging).
   6. The Bio-M System includes means to prevent signal saturation.
   7. The Bio-M System includes means to reduce artifacts (such as artifacts caused by movement: e.g., muscle contraction, respiration).
2. The Bio-M System can provide HR:
   1. The HR range is 30-220 Beats per Minute (bpm).

Additional Cardiovascular

1. The Bio-M System can provide an estimate of continuous Systolic BP:
   1. The estimate of continuous BP accuracy is within ±5 mm Hg or 4% (whichever is greater) compared to an accepted standard for this type of measure.
   2. The BP range is 70-260 mm Hg.
   3. The resolution of the BP estimate is of 1 mm Hg or better.
2. The Bio-M System can measure Peripheral SpO2:
   1. The Bio-M System provides a measure of the Peripheral SpO2 with an accuracy level equal or better than that of a commercial SpO2 or Pulse Oximeter certified by Health Canada or the Food and Drug Administration (FDA).
   2. The Peripheral SpO2 can be acquired at a sampling rate of 64 Hz or higher.
   3. The Peripheral SpO2 range is between 30 to 100%.
   4. The Peripheral SpO2 resolution is 1% or better.
   5. The Bio-M System sensor for Peripheral SpO2 can offer flexibility for sensor site (e.g., forehead, ear lobe, toe and finger - flexible type that can be wrapped over the index finger nail without compromising dexterity).

Respiratory Measures

1. The Bio-M System can measure Respiration:
   1. The detected RR is within 5% of the actual RR.
   2. The Respiration signal is sampled at a rate of 128 Hz or higher.
   3. The RR range measured is 2-90 respiration cycles per minute.
   4. The RR resolution is 1 respiration cycle per minute or better.
2. The Bio-M System can provide breath by breath Tidal Volume (VT):
   1. The VT range is 200-7000 ml.
   2. The target VT range is 100-7000 ml.
   3. The VT resolution is 20 ml or better.
3. The Bio-M System can provide VE:
   1. The VE range is 1-90 L/min.
   2. The VE resolution is 0.02 L/min or better.

Activity Measures

1. The Bio-M System can measure a crewmember's full-body orthogonal triaxial acceleration:
   1. The measure of acceleration axes has a range up to ±16 g.
   2. The measure of acceleration axes has a sampling rate of 64 Hz or greater.
   3. The measure of acceleration will not be affected by the absence of gravity.
   4. The acceleration measure resolution is of at least 0.01 g.
2. The Bio-M System can measure body, or wrist, or arm, or ankle actigraphy (or a combination of strategies).
   1. The actigraphy range is 0.03 to 13 g.
   2. The actigraphy resolution is at least 0.01 g.
3. The Bio-M System can measure cadence:
   1. The cadence range is 0-240 Repetitions or Revolutions per Minute (RPM).
4. The Bio-M System can measure step-to-step step count.

Skin Temperature

1. The Bio-M System can measure skin temperature (preferred forehead or torso):
   1. The accuracy of the measured skin temperature is within ±0.1°C compared to a recognized accepted standard for this type of measure.
   2. The temperature measurement range is between 10-50°C or larger.
   3. The measured temperature resolution is 0.1°C or better.

Appendix B: Guidelines on ISS investigations using the LSRS

Flight experiment proposals must represent mature studies strongly anchored in previous or current ground-based or flight research. Ground-based research must represent one component of a flight experiment proposal and must be limited to activities that are essential for the final development of an experiment for flight, such as definition of flight procedures, testing of experiment hardware and control activities for the flight experiment.

The presence of both the Bio-A and Bio-M systems on board the ISS provide the opportunity to monitor the efficacy of specific countermeasures in near real-time. Investigators are encouraged to propose projects that would benefit from this new capability to assess previous or new countermeasure efficiency through regular in-flight measurements.

While this is not part of the evaluation process of this AO, applicants are encouraged to propose the measure of additional parameters that would fall outside current instrument performance. The provided information will be used as part of our continuing improvement program and may lead to an improved version of the system for future users.

There are certain experimental procedures that, while not impossible to perform, are difficult to implement during ISS operations. Those procedures/requirements that may be difficult to accommodate include:

• Requirements for conditioned stowage (i.e. other than ambient temperature) that exceed the capabilities (i.e. Temperature ranges, volume) of the equipment identified on the conditioned stowage web site.
• Requirement for more than 14 human subjects.
• Overly invasive or complicated procedures that may hinder crew consent.
• Total pre-flight Baseline Data Collection (BDC) requirements of more than 5 hours.
• More than 2 hours of BDC required within 3 months of launch.
• Pre-flight BDC testing requirements within two months of launch.
• In-flight procedures that require a high degree of proficiency and training prior to crewmember launch.
• Two or more hours of testing required within the first three days of landing.
• More than three hours of total testing in the first week post-flight.
• Strenuous or provocative sessions on R+0 or R+1 (i.e. immediately after landing, or on the first day after landing. Usually, it is difficult to have access to the crew until 24 hours post- landing.
• More than three complicated in-flight sessions involving multiple pieces of equipment. (e.g., requires set-up of multiple pieces of equipment, followed by testing of more than 2-3 hours).
• A single session with one crewmember requiring 4 hours in one day.
• Crew activity that must be performed daily or more than once a week.
• Very precise/inflexible timing requirements for sessions.
• Extended, continuous activities over multiple days that could interfere with other operations.

Data collected by Medical Operations, related to maintaining and monitoring of crew health, is in principle also available for scientific use, provided that informed consent is given by the research participant.

Appendix C: Structure for the detailed project description

This document should contain sufficient detail to enable a reviewer to make informed judgments about the overall merit of the proposed research and the probability that the investigators will be able to accomplish their stated objectives. It should clearly indicate the relationship between the proposed work and the research emphases defined in the announcement. The development of a clear hypothesis, along with the available data evidence, should be emphasized. In addition, the proposal should provide evidence of completed or planned ground research to justify the flight experiment.

The cover page of the description must contain the title of the proposal, the name of the PI and the legal name of the organization requesting the Contribution. The detailed description (maximum of 20 pages, excluding references) must include the following material:

1. Summary (1 page)
2. Background
3. Relevance to the announcement priorities (1 page)
4. Research hypotheses
5. Methodology
6. Research team's experience, roles and responsibilities
7. Requirement for in situ analysis
8. Training plan
9. References

The document must be provided in a commonly used format (.DOC, .DOCX, .PDF, .RTF, .TXT), 12pt type face, letter sized paper and 1" margins.