Towards rapid, high-throughput and cost-effective evaluation of viral vector efficacy: Rapid image pattern analysis from microfluidic cell cultures us

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Lentiviral Vector (LV) manufacture is characterized by expensive development, resulting in high treatment costs of up to $500,000 per patient treatment. Monitoring of critical quality attributes during viral vector manufacture, such as the infectivity of the vector, is vital. Current gold standards for viral vector titering rely on infectivity assays. They allow estimating the number of infectious particles contained in a sample through the infection of cells. Currently, these assays are carried out in micro well plates, thus limited to end-point monitoring through expensive processes. Furthermore, the liquid volumes are still large for high-throughput analysis, and automation capabilities are limited. To facilitate personalized gene therapy treatments and decentralizing manufacturing, a microfluidic device which operates with tiny volumes and which provides real time assay data was developed in our labs. In this project, the microfluidic device will be used to perform infectivity assays and bench-mark them against the industrial gold standard. The technology developed thus far uses a fluorescence approach to detect LV titer but new modalities can be implemented. Artificial Intelligence algorithms will be developed enabling automated infectivity assays. This will combine microfluidic technology with advanced image analysis routines and machine learning algorithms to allow the development of high throughput infectivity assays, laying the foundations for future work where this platform can optimally assess patient to patient variability of viral vector uptake.