Enabling Technologies to Accelerate Development of Oral Biodevices (R41/R42 Clinical Trial Not Allowed)

Purpose

This Funding Opportunity Announcement (FOA) invites applications that propose transformative engineering solutions to technical challenges associated with new development, substantial optimization of existing technologies and clinical translation of intraoral biodevices. Proposed technologies are expected to advance development of oral biodevices to clinical use, including but not limited to: precision medicine-based detection, diagnosis and treatment of oral and overall health conditions, and measurement of patient functional status and clinical outcome assessment. Areas of interest in this FOA include engineering approaches that allow integration of electronic, physical, and biological systems essential to the development of functional biodevices that are safe and effective for detection, diagnosis and treatment of oral and systemic disease. Products of this research will be proof-of-concept prototype biodevices, dedicated biosensors, associated core technologies and integrated approaches that enable development of safe and effective intra-oral biodevices intended for specific clinical applications. To streamline the development of oral biodevices that advance precision medicine-based approaches in clinical practice, this FOA encourages interdisciplinary collaborations across engineering, multifunctional sensors, pharmacology, chemistry, medicine, and dentistry, as well as between academia and industry.

Background

Disease diagnosis relies on a variety of laboratory-based assays including microscopy, tissue and microbial cultures, immunoassays and nucleic-acid amplification. While development of many of these highly-sensitive and robust assays has revolutionized evidence-based diagnostics, in many situations, a continuous, non-invasive real-time assessment would offer additional significant advantages for delivery of evidence-based care.  

Advances in biomaterial sciences, biomanufacturing, microfluidics and nanotechnology are leading to the development of next generation simple, fast and reliable diagnostic devices, including biosensors, capable of real-time, continuous and noninvasive quantification of biological, chemical, and physical processes for health surveillance and rapid disease detection. Amperometric-, optical-, surface plasmon resonance-, enzymatic-, DNA-, phage-, and bacterial-based biosensors have shown significant promise for detection of a broad spectrum of biological analytes in medical laboratories and food bioanalysis.  Such technologies could be utilized in biosensors as well.  Additionally, biosensors are increasingly being used to augment therapeutic drug regimens by strengthening patient compliance. As biosensor technologies continue to advance towards smaller more accurate and application-specific integratable, wearable, and embeddable devices, these devices will become important components of medical diagnostics and monitoring that will allow for obtaining clinically-relevant outputs and endpoints indicative of health status, disease progression, and patients’ compliance with treatment regimens.

Gaps and Opportunities

This FOA seeks to address key technical barriers affecting the safety and overall performance of biodevices specifically designed to function within the oral cavity. While the oral cavity offers unique advantages to access real-time, continuous, noninvasive, physiological measurements, the oral environment presents specific design and performance requirements that need to be addressed according to target clinical applications. Therefore, a systems engineering approach is needed to address major design challenges imposed by the oral environment, including: mastication forces, varying pH levels and temperatures, oral flora, adhesion to wet intraoral tissues, interference with speech, breathing and nutritional intake, material biocompatibility, and prevention of injury to oral tissues.

The oral cavity is an attractive site for developing integrated biosensor-drug delivery-mobile notification devices that would improve treatment of many oral diseases and, in certain cases, would enable systemic delivery of therapeutics in an effective and patient acceptable manner. Such systems would enable precise dosing of medications, enhance medication compliance, and reduce drug-related side effects. Pairing of pharmaceutical products with delivery devices requires close attention to their design, function, and efficacy. An oral biodevice with combined sensing and drug delivery features must consider many different design factors including, drug release profiles, performance requirements dictated by the oral environment and patient acceptance. Design of the release profile for integrated biosensor-drug delivery systems would depend on the condition being treated along with specific parameters of the patient’s metabolism, genetics, epigenetics, diet, and intake of other medications.

Specific Objectives

This FOA seeks to advance meaningful development and substantial optimization of enabling technologies and systems engineering approaches to accelerate innovation and translation of intraoral biosensors and biodevices to clinical practice. Areas of interest include, but are not limited to: Improving the quality of biocompatible materials for optimal device functionality, preventing or minimizing material biofouling and advancing low-power/miniaturized/flexible electronics. In addition, this FOA will support advancing the capabilities of long-term power cells, integrating biosensors with implantable devices and mobile notification systems, securing wireless data transmission and developing technologies that enable reliable adhesion of biosensors and biodevices to wet intraoral tissues. 

Examples of research projects may include, but are not limited to the following:

Enabling Technologies

• Development of highly-sensitive and selective biodevices utilizing efficient transducing elements and biosensitive materials to detect small quantities of biomolecules.
• Development of micro/nanoscale biodevices for detection of biomolecules and/or events resulting from enzymatic reactions.
• Development of high fidelity, self-powered, stand-alone, biodevices with secure wireless data transmission to allow adequate quantification and analysis of clinically relevant measures.
• Development of label-free affinity biosensors with demonstrated selectivity, reproducibility and accuracy to chosen analyte(s) tailored to specific applications.
• Optimization of interactions between nanomaterials and biomolecules on the surface of electrodes, and development of biosensor arrays to improve reproducibility and accuracy of molecular detection or simultaneous detection of multiple validated biomarkers.
• Improvement of strategies to ensure materials’ biocompatibility, device reusability, minimization of device biofouling, enhancement of device shelf-life and improvement of device adhesion to wet intraoral tissues.

Systems Integration and Interoperability

• Development and validation of fully-integrated biosensor-based systems that bring together components of sample preparation and analyte detection with interoperable digital health systems / internet-of-things (IoT) platforms / drug delivery systems / end-user functionality.
• Establishment and validation of biological and engineering solutions for system-level tasks in sensing, interfacing, and designing control processes to improve performance of multi-functional sensors for intraoral applications.
• Development of control systems using dynamically interfaced intraoral biosensors and actuators for flexible, highly-controlled drug release, electrical stimulation and other therapeutic outputs.
• Implementation of smart biodevices that support clinical decision-making for timely assessment and effective treatment of medical conditions.
• Integration and validation of biosensors and processing technologies in embedded, continuous, intraoral diagnostic systems with individualized signal conditioning components for diagnostic and trend-detecting algorithms.
• Miniaturization and integration of biosensor components within an enclosure or a framework adequately designed to conform comfortably to the oral cavity.

Projects that are not appropriate for this FOA include:

• Biomarker discovery

See Section VIII. Other Information for award authorities and regulations.