SBIR-STTR Award

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to develop a resonant sensor system to monitor cell viability in small bioreactors. Cell factories are responsible for producing more than $150B worth of cell therapies, protein therapies, industrial enzymes, and small molecules each year. At the development phase, there are few technologies to monitor viable cell concentration, a critical quality attribute in a large array of bioreactors. Current methods to monitor cell viability are labor intensive, expensive, and can compromise quality. The proposed technology could be embedded into the walls of disposable flasks and bioreactors to provide real-time measurement of viable cell concentration. This could enable substantial "big data" improvements for bioprocess developers, clonal selection, and small batch production. This STTR Phase I project proposes to demonstrate passive, wireless sensing of viable cell concentration with resonant sensors. Dielectric probes are used in industry to correlate culture capacitance to viable cell concentration in large culture volumes. In this proposal, the change in culture capacitance in small culture volumes could be wireless reported with a passive sensor embedded as part of the disposable culture flask or single-use bioreactor. In this form factor, it would never make contact with the cell product, would be wirelessly implemented, and would have potential to be easily multiplexed. Technical objectives for this work are 1) determining the extent of confounding signal effects from movement, media composition and temperature; 2) building a Bluetooth enabled reader pad for implementation in an incubator; and 3) developing an algorithm that translates the complex resonant sensor amplitude and phase data into simple parameters that can be used to track viable cell concentration. In addition, the plan is to model and test the effect of resonator geometry, material composition, and sensor placement. The goal is to produce a robust sensor system for cell viability to test in real culture conditions on numerous cell types. 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.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is the creation of a sensor system for cell-based manufacturing of such products as biologic therapies, food ingredients, and bio-based materials. These sensors will overcome current limitations for tracking critical cell growth data, which requires manual sampling with slow turnaround times. This system will enable better predictive growth models for improved production process development and will lead to better decision-making on cell type and culture conditions to produce biologic material. Better performance at this stage leads to potentially significant savings during the manufacturing lifetime of the drug. This Small Business Innovation Research (SBIR) Phase II project is focused on developing a wireless sensor system to address the need of continuously monitoring viable cell density during biomanufacturing. Many industries use cells for production, but the initial focus is upstream development of cell therapies and biologics. Central to this development is tracking the growth of cells in a variety of small-scale, single-use bioreactors to determine key event points for feed and harvest. Current methods rely on infrequent sampling and off-line counting due to the volume required, risk of contamination, and cost. The central research objective is to develop methods for standardized sensor and reader fabrication and quality testing for calibration studies in commercially-relevant environments and systems. The proposed project will develop: 1) sensor stickers that are applied to the exterior of culture vessels, 2) readers that interrogate the sensor, and 3) algorithms to convert the sensor signal to cell count and push notifications to operators. 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.