What if the bottleneck in cell line development isn’t how many clones you screen, but how you track them?

Cloning workflows have long relied on brute force: screen more cells, automate harder, and hope that small-scale performance predicts manufacturability. But too often, the “perfect” clone in a 96-well plate turns into a dud when it reaches the bioreactor. That disconnect costs time, money, and promising therapies.

This week, host David Brühlmann welcomes Kent Rapp, Co-founder and CEO of Biolinco, an entrepreneur who’s turning the classic approach to cell line development inside out. Drawing from his background in chemical engineering and his work in biomanufacturing at Johns Hopkins University, Kent teamed up with DNA barcoding experts to pioneer a new workflow: barcode every cell, pool them, and track their true performance in the environment that matters.

Topics discussed:

• The pitfalls of brute-force screening in traditional cell line development (03:05)
• Kent’s background and how he was drawn to combine science, startups, and biomanufacturing (04:37)
• Overcoming discrepancies between small-scale and large-scale screening environments (08:30)
• How DNA barcoding allows for high-resolution, pooled clone screening (10:34)
• Sensitivity advantages of sequencing over plate-based detection (14:21)
• Methodology for tracking and recovering individual high-performing clones from pools (15:13)
• Impact on speed and workflow efficiency in cell line development (17:31)
• Regulatory and safety considerations related to DNA barcodes in cell lines (19:04)

Smart insight: According to Kent, biotech as an industry has a tendency to "automate problems instead of solve them". Rather than addressing the root causes—like lack of meaningful measurements at relevant scales—companies often throw more robots and more plates at the issue, hoping brute force will finally yield the magical clone. But real process improvement requires a rethinking of what is being measured and how those insights are generated—not just a higher throughput of the same flawed assay.

If this got you rethinking how you screen clones, you'll want these next. We've tackled cell line development, high-throughput screening, and the art of spotting manufacturable candidates early from a few different directions — here are four worth queuing up.

• Episodes 117 - 118 : Cell Line Development Secrets: Eliminating Critical Bottlenecks for Faster Timelines with Andrea Gough
• Episodes 09 - 10: Revolutionizing Cell-Line Development: Unleashing the Power of Nanopens and Microenvironments with Tanner Nevill
• Episodes 123 - 124: Manufacturability: Why Most Protein Candidates Fail (And How to Pick Winners Early) with Susan Sharfstein
• Episodes 115 - 116: Revolutionizing Biologics Development with Hyper Throughput Screening and AI with Jeremy Agresti

Connect with Kent Rapp:
LinkedIn: www.linkedin.com/in/kent-rapp
Biolinco website: www.biolinco.com

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

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