Scaling up and scaling down
Lesson 5 of 6 · Methods at the bench
1 · Learn the move · Recipe pattern
Volumes scale linearly; physics does not. Doubling a reaction doubles the reagents, but a tenfold scale-up changes mixing time, heat transfer, surface-to-volume ratio, gas exchange, and what your centrifuge can even hold - and a tenfold scale-down turns pipetting error from noise into signal. The recipe: recompute every step's quantities showing the arithmetic, then mark each step LINEAR or NONLINEAR, where NONLINEAR means the straight multiplication is an assumption, not a fact, with a note on what actually governs it. Pilot at an intermediate scale before committing material. And scale changes your hazard picture - ten times the solvent is not the same conversation with EHS as the bench-scale version, so the EHS check reruns at the new scale before the first run.
Scale this protocol from [current scale] to [target scale]: [paste]. For every step: recompute quantities, show the arithmetic, and mark LINEAR or NONLINEAR. For each NONLINEAR step, state what actually governs it and what to watch in a pilot. Flag every vessel, rotor or instrument limit the new scale hits. List hazard-relevant changes (solvent volumes, exotherm potential) as questions for EHS - do not clear them yourself. Recommend an intermediate pilot scale.
2 · Your turn. You write the prompt
Your 50 mL bacterial expression culture needs to become 1 L to feed a structural biology collaboration. Same construct, same media, same induction - twenty times the volume. The last person who scaled a culture in this lab lost two weeks to an aeration problem nobody had flagged.
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