Low volume transfers with large capacity syringes

Curious about strategies for using high capacity pipettors for low volume transfers.

For context, I’ve got a 384 Pico method I’ve developed that uses a 1200µL 96-multichannel for all steps. I’ve done a lot of LC development, but there are a few issues that seemed interesting:

  • Multidispensing low-medium volume over many iterations
    It seems that liquid pressure affects volume dispense significantly. I have 50µL x 12 dispenses and had to apply an offset to each dispense to increase delivery for the firs few aliquots and decrease delivery for the last few.
  • Super-low aspiration-dispense
    This is madness - but 2µL transfers are hard with 1200µL syringes (who’d of thunk). Reverse pipetting works wonders when aspirating, but depends on volume at the reagent/sample source.

The 2µL transfer is one I have a general strategy question for as well. I’ve run into some strange issues where aspirating a STAG/Blowout volume will prime the tip with negative pressure which will aspirate liquid on contact, leading to additional volume being aspirated on top of desired volume. Secondly, the surface tension (aqueous, water-like) of the liquid in well is difficult to overcome with such low pressure differential. If the volume aspirates it’s accurate, however I’ve seen about 1/48 samples not aspirate.

I’ve got some working LC’s after a few days work, but I’m open to feedback on how others have solved low volume transfers like these - especially in bulk where a multichannel is necessary.