PacBio Overloading Simulations
Summary: On PacBio instruments, if you don’t care about run time, overloading the chip with multiple polymerases per ZMW seems like the optimal solution. However… this can increase runtime. PacBio have likely had to balance total chip throughput against runtime to find a product-market fit.
PacBio overload their chips, loading multiple polymerases per ZMW1. They then need to wait for all but one polymerase to die off until sequence data can be generated. Polymerase “death” isn’t due to cumulative damage2. So at every time point, there should be a roughly equal probability of the polymerase dying.