May the (Dispensing) Force Be with You
Exploring the Common Forces Behind Liquid Handling
Intro
Manual pipettes typically use air displacement to aspirate and dispense liquids. Some automated liquid handlers use this same principle, but they can also use other technologies to dispense a range of volumes and liquid classes. Let’s explore three different forces used in automated liquid handlers: air displacement, positive displacement, and acoustics.
Air Displacement
Like in a manual pipette, air displacement in an automated system applies force to a pocket of air between a piston and the liquid. The air displaced is equal to the volume of liquid handled. Instead of your hand providing the force on the piston, a robot does it for you.
Pros:
Best for larger volumes (up to 5mL) dispensed with a low CV (<5%)
Air pocket and filter tip provide enhanced sterility
Works best with aqueous solutions
Can perform mixing steps
Better sample tracking
Cons:
Cannot accurately dispense liquids below 1uL
Does not handle viscous liquids well
Multi-dispense and serial dilution require many specialized tips
More dead volume required; harder to use precious samples without waste
Common liquid handling platforms like the Tecan Fluent, Agilent Bravo, Beckman Biomek, and Hamilton STAR use air displacement. The Tecan Fluent can also use liquid displacement.
Positive Displacement
Positive displacement is slightly more accurate than air displacement, at the cost of increased cross-contamination risk, as the piston directly contacts the liquid.
Pros:
More accurate dispensing below 1uL; can also handle higher volumes up to 1mL
Handles a wider array of liquid classes with little optimization
Contamination risk mitigated with disposable tips
Can perform mixing steps
Sample tracking
Cons:
Disposable tips often more expensive than air displacement tips
Less common technology with less support available
Some steps require many tips, increasing cost
Higher dead volume
The Formulatrix F.A.S.T. Liquid handler is a good example of this technology.
Acoustic Displacement
Acoustic liquid handling uses sound waves to dispense small droplets of liquid, offering the lowest dispensing volumes possible: in the picoliter range (1×10⁻¹² liters)!
Pros:
Accurate small volume dispensing in the sub-nanoliter range, little to no dead volume
Non-contact dispensing with a wide range of liquid types
Uses less consumables; small volumes make serial dilution almost obsolete
Cons:
Cannot aspirate with acoustics
Specialized consumables often loaded by hand, making sample tracking difficult
Larger volumes take longer to dispense dropwise
The Scienion SciFlexxarayer dispenses volumes down to about 11pL using piezoelectric technology! Reaching that kind of concentration manually in a well is only possible with serial dilution which can’t reach the same level of accuracy as an automated system like this.
Conclusion
Understanding how liquids are dispensed will help you choose the right liquid handler for your needs. By weighing the pros and cons of air displacement, positive displacement, and acoustics, I hope I’ve helped you in your lab automation journey. It’s important to be weary of biased data from vendors, but I can say from experience that the CVs advertised are pretty close to the real thing. Two of my favorite small volume liquid handlers, the Tecan D300 and the Dispendix IDOT, don’t use any of these technologies. I’d like to take a deep dive into these versatile instruments in my next post.
