SBIR-STTR Award

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to digitize the human sense of smell and develop a platform to create "humanized mice" that that express any human odorant sensor in the nose of a mouse. Tools have been developed to determine the unique odor codes for each individual odor mixture that exists today ranging from the fragrances in a perfumer's palette to the Chardonnay in your wine cellar. Such an olfactory code will allow flavor and fragrance companies to predict the "smell" of certain odor mixtures, and to engineer new compounds in a rational and more streamlined manner. This technology will have a significant commercial impact on existing consumer products, including food, personal hygiene, household products, and perfumes, by offering a solution to more efficiently design pleasing scents and flavors or to formulate compounds that block repulsive odors. In addition, the proposed chemical detector platform under development to generate this olfactory code has additional applications as a biosensor. It may be used to generate disease-specific chemosignatures identified in bodily fluids like urine, sweat or blood, which may have application in clinical diagnostics and biomarker discovery. This SBIR Phase I project proposes to use human odor sensors produced in their native environment, an olfactory sensory neuron, and develop an ex vivo biochemical assay to screen for odor sensor activation in a quantitative way. Since human odor sensors (odorant receptors) have proven to be exceptionally difficult to express in vitro, high-throughput screening of odorants using conventional pharmaceutical methods have not been possible to date. As such, only 10% of all human odorant sensors have been linked to their single odor. The preliminary data show that the in vivo expression of human odor sensors in mouse olfactory sensory neurons are functional. The objective of this project is to show that in vivo expressed odor sensors, when removed from their biological model system, maintain their functionality (i.e., ex vivo). A secondary objective is to demonstrate that several types of odor receptors, each with an accepted odor profile, will respond as predicted when analyzed ex vivo using a biochemical assay measuring direct activation of odorant receptors. Successful assay development will allow the generation of a viable platform that may be expanded with additional odor receptors to further decode human olfaction.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to ultimately develop a nose-on-a-chip to establish the first-ever digital database of smell. By interfacing the biology of the human nose with a read-out platform, it will be possible to decode the human sense of smell and open up new possibilities. Such a nose-on-a-chip and its associated smell database has multiple commercial applications in the fragrance and flavor industry including increasing the efficiency of developing aroma chemicals for food, personal hygiene or household use, and fine perfumes. Also, it may be possible to identify specific malodor receptors and developing compounds that block repulsive odors or modulate olfaction (boost smell capacity and/or suppress odor cravings). In addition, the smell database can be employed to develop algorithms that predict how new aroma chemicals will smell before making them. There is an additional opportunity for the nose-on-a-chip in the healthcare industry when applied to sniff out disease-associated odors, such as Parkinson's disease. Odor-based disease detection may revolutionize biomarker discovery and may have a significant impact on R&D spending in the pharmaceutical industry and ultimately decrease treatment cost for patients.The intellectual merit of this SBIR Phase II project is to produce an odor-specific nose-on-a-chip assay containing a subset of odorant receptors that can report the presence of a specific odor (odor MS1) and its derivatives. This minimal viable platform is based on a well-validated need in the fragrance and flavor industry and needs to demonstrate sensitivity, specificity, selectivity and intensity (S3I) of odor activation. The goals are to identify a set of high-affinity odor MS1 receptors, generate engineered mice for each receptor through this validated platform technology and demonstrate S3I using an established ex vivo bio-assay. Engineered mice form the basis of the proposed commercial platform. They are the bioreactors producing the olfactory extracts that are used in the ex vivo bioassay and, ultimately, are integrated with a silicon chip. As such, optimized generation of mice is key to cost-efficient scaling of the proposed commercial chips and is a primary objective of the project. The plan is to develop a high-throughput method of generating any receptor in mice. Then, the goal is to develop an optimized gene-targeted line that will serve as a standardized template for future knock-ins of any odorant receptor gene, providing a streamlined, standardized and scalable method to ultimately establish the complete library.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.