Biodefense

Draper has a 25+ year legacy focused on development of in vitro human tissue Microphysiological Systems (MPS). We employ advanced, cross-cutting solutions to improve our understanding of how CRBNE threats affect the body and to predict the safety and effectiveness of drugs, vaccines, and antibody-based treatments. Draper advancements in the field have resulted in MCM evaluation solutions that leverage human tissue MPS (or organ-on-chip) platforms, immune system models, molecular and cellular assays, omics-based technologies, and advanced analytical methods. These innovations enable in-depth assessment of threat agents and MCM interventions.

Draper employs a suite of capabilities and technologies to assess CBRNE threats, enabling assessment of the host response to injury, infection, disease progression, and inflammation. These tools also enable the evaluation of repurposed or novel MCMs for efficacy, biomarker discovery, correlates of immune protection, and toxicology and safety prediction.

We aim to develop streamlined and prognostic MCM solutions that can complement or replace animal models in CBRNE research and testing and enable the evaluation of MCMs for CBRNE threats. This goal directly aligns with long-term requirements established by the U.S. Congress and the FDA.

Drug and MCM candidates often fail to demonstrate adequate efficacy and safety as the FDA regulatory process progresses from animal models to human clinical trials. Additionally, the accepted preclinical animal models and human clinical trials have embedded time and cost constraints that affect MCM development timelines for critical CBRNE threats.

To date, we have fielded 10 distinct single-organ tissue models, separate models for organoids, solid tumor, and revolutionary multi-organ platforms to model the holistic and interconnected function of human organ systems. Designed for seamless integration into standard laboratory equipment and drug evaluation pipelines, our technologies maximize flexibility and throughput. With parallel, integrated sensors, our platforms deliver far more high-quality data than other preclinical models, making preclinical testing for drug development more predictive and enabling novel drug discovery avenues.

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High-throughput platform. The PREDICT96 system is composed of a microfluidic culture plate with 96 individual bi-layer microchannel-based tissue culture units. Each unit is comprised of an apical and basal channel separated by a Transwell^®-like membrane, in a standard 96-well plate format (Figure 1 B). The platform conforms to the SBS standard microplate footprint, enabling compatibility with high-throughput screening imaging modalities and other industry-standard equipment.

Figure 1.  PREDICT96 System Architecture

Dynamic flow control. A recirculating pneumatic perfusion system driven by 192 microfluidic pumps in the lid enables independent operation in the apical and basal chambers of each of the 96 tissue units, providing physiological levels of fluid shear stress (Figure 1 C), as well as enabling accumulation of important signaling molecules and metabolites. 

Real-time sensing. Functionalized, stainless steel pump sippers facilitate fluid movement in the system and concurrently serve as integrated electrodes for near real-time sensing (TEER, O2). The system can be controlled remotely outside of an incubator using proprietary software (Figure 1 D).  These real-time sensors reduce operator contact and intervention with the systems, increasing safety and mitigating potential sources of cross-contamination.

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The Biomedical Advanced Research and Development Authority (BARDA) and Draper have executed an Other Transactional Agreement (OTA) that will allow advancements to be made regarding the scientific understanding of illness/injury resulting from exposure to a broad range of chemical, biological, radiological, nuclear (CBRN) threats (including high-priority pathogens and toxins), along with emerging infectious disease threats, and evaluate medical countermeasure (MCM) treatments. One project funded under the OTA is a Respiratory Infectious Disease MPS Tissue Model.

The overall objective of the project is to develop solutions that will enable evaluation of the drivers of immune-mediated SARS-CoV-2 pathogenesis in the body. Draper’s high throughput MPS platform, PREDICT96, will be used to model the immune/inflammatory response to infection and real-time BSL-3-ready robust real-time sensor integration. The project will also investigate and characterize the mechanisms of infection and inflammation across diverse disease and demographic populations such as age, sex, and presence of co-morbidities. Platform enhancements will include scaleup and system integration of TransEpithelial Electrical Resistance (TEER) and Reactive Oxygen Species (ROS) sensors, with a focus of demonstrating operational functionality in a high-containment, BSL-3 environment. Additionally, RHM will advance plate manufacturing capabilities, including utilization of roll-to-roll and injection molding processes. 

A final task will include screening of medical countermeasures, starting with known efficacious and non-efficacious treatments. The long-term aim is to develop platform capabilities that will allow fast and accurate evaluation of SARS-CoV-2 viral infection in human tissue, disease progression, and immune/inflammatory response. Finally, this project will improve our scientific understanding of human demographic and disease drivers by correlating diverse donor characteristics with infection response.

This project has been funded in whole or in part with federal funds from the Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under OTA number: 75A50123C00042. 

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The Biomedical Advanced Research and Development Authority (BARDA) and Draper have executed an Other Transactional Agreement (OTA) that will allow advancements to be made regarding the scientific understanding of illness/injury resulting from exposure to a broad range of chemical, biological, radiological, nuclear (CBRN) threats (including high-priority pathogens and toxins), along with emerging infectious disease threats, and evaluate medical countermeasure (MCM) treatments. One project funded under the OTA is a Radiation Injury MPS Tissue Model.

The overall objectives of the program are to study the natural history of gastrointestinal acute radiation syndrome (GI-ARS), to identify biomarkers and drug targets from multi-omics analyses, and to assess drug candidates in vitro and in vivo. Draper’s high throughput MPS platform, PREDICT96, will be used to create primary human GI microvascular-immune and epithelial-immune models that will be used to elucidate the natural history of radiation damage by systematic exposure to radiation doses analyzed by cell type and through time. 

This model will advance the development of an MCM evaluation platform that consists of vascular-immune and small intestine-immune MPS models, phenotypic assays, omics-based technologies, advanced analytical methods for biomarker discovery, and biomarker correlation with animal models, all specifically focused on irradiation-induced damage to the body. An additional goal of the work is to identify potential repurposed therapeutic drugs and demonstrate the non-clinical workflow using the Draper PREDICT96 platform, followed by correlation with animal studies to evaluate efficacy of promising MCM candidates.  

This project has been funded in whole or in part with federal funds from the Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under OTA number: 75A50123C00042.

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