Advancing the State of Knowledge
RFA4 will develop a suite of NIR II/SWIR (1-2µm wavelengths) emissive materials that will enable breakthrough biosensing and imaging applications. To capitalize on the opportunities afforded by NIR II/SWIR bio-imaging, this RFA brings the expertise of a multidisciplinary team of material scientists, chemists, and biologists to establish a unique collection of compounds with the potential to transform research and diagnostics. Our approach is fundamentally distinguished by the utilization of modular approaches, new chemistries, and target molecules whose spectral properties can be precisely controlled and integrated with sensing modalities. To facilitate practical implementation of NIR II/SWIR fluorophores, we will use computational methods to predict and propose candidates for experimental development of novel molecules and water-soluble polymers with low cytotoxicity and enhanced photostability. These initial fluorescent targets will be covalently attached to biomacromolecules (i.e., proteins and antibodies) for biosensing applications. Further modifications to the molecular framework of these novel molecules will afford materials capable of responding to physiological relevant analytes.
The collection of materials developed in this RFA will overcome the limitations of conventional fluorescent and tomographic techniques, revolutionizing capabilities within diverse fields. The proposed research activities will span molecular design to testing of compounds in cell culture and animals. To establish the capacity of these materials, efforts will target properties of biological systems that will be of interest to both basic research and the clinic.
Research objectives and tasks (defined below) have been developed to address the following research questions:
4.1 What are the electronic and physical interactions that will enable emission with high quantum efficiency in the NIR II/SWIR in small molecule and polymer fluorophores in biological systems? What are the extrinsic mechanisms associated with low efficiencies within these spectral regions in the context of biological/aqueous environments? What are the underlying physical and chemical principles that will lead to conceptual designs for new molecules and materials?
4.2 What bioconjugation strategies can be used to attach NIR II/SWIR emissive material to proteins, DNA, lipids, etc. that retain the native structure of these biomolecules to create new capabilities for deploying biomarkers and expand multiplexing options?
4.3 Can NIR II/SWIR materials be developed for biosensing? What are the molecular design considerations for generating molecules for detecting extracellular and intracellular analytes? Can a desired distribution in biological systems be achieved through molecular engineering?
Goals and Objectives
Goal 4.1: Determine the effects of molecular structure and environment on the photophysical properties of NIR II/SWIR small molecule and water-soluble polymer fluorophores to enable new design strategies for emissive materials.
Objective 4.1.1: Establish predictive protocols to understand the effect of energy gap between the excited and ground state of NIR II/SWIR small molecule and polymer fluorophores.
Objective 4.1.2: Establish predictive protocols to understand the presence of vibrational states in the surrounding matrix and their coupling with the excited electronic states as well as the role of environment on emitter stability and brightness.
Goal 4.2: Establish bioconjugation strategies for classes of fluorophores which exhibit non-overlapping NIR/SWIR emission signals for biosensing.
Objective 4.2.1: Tune the emission bands of fluorophore materials based on target dyes for the NIR II/SWIR region.
Objective 4.2.2: Develop and apply synthetic routes to covalently attach NIR II/SWIR fluorophores to biomacromolecules for biosensing applications.
Goal 4.3: Design NIR II/SWIR bioprobes for dual sensing and imaging.
Objective 4.3.1: Synthesize NIR II/SWIR bioprobes capable of an “off/on” fluorescent emissive response to physiological relevant analyte.
Objective 4.3.2: Synthesize NIR II/SWIR molecules with enhanced water solubility and cell-permeability.