Many biotech firms default to increasing throughput (e.g., screening more cells) via automation to solve development challenges. This brute-force approach often masks underlying issues, such as the disconnect between small-scale screening and large-scale manufacturing environments, rather than addressing them strategically.
Conventional cell line development screens clones in small-scale formats like 96-well plates. This environment starkly differs from the large-scale, controlled bioreactors used in production, leading to clones that perform well initially but fail when scaled up, creating a costly and predictable development bottleneck.
By labeling each cell with a unique DNA barcode, all clones can be grown together in a single, manufacturing-relevant bioreactor. This shifts the core challenge from laborious individual cell measurements to a high-throughput sequencing and data analysis task, dramatically increasing efficiency and data richness.
The challenge with pooled screening is isolating the single best clone. A novel approach uses a CRISPR activation system that specifically targets the winning clone's unique DNA barcode. This activates a selectable marker, enabling the high-precision extraction of the desired cell line for monoclonal expansion.
Traditionally, vector design and cell line development are sequential steps requiring intermediate tests. By screening a mixed pool of candidates with DNA barcodes directly in a bioreactor, these stages can be overlapped, accelerating the timeline from initial design to identifying a high-performing manufacturing clone.