Comparing automated liquid handlers to find your lab’s solution? The guide part 1

If you are anything like me, when faced with a task you know little about, you procrastinate until it's urgent and then run on adrenaline to get it done. Whether this is how you work, or you want reassurance that your carefully prepared research into automated liquid handling options is on the right lines, read on.

Where to start? Google and your peer network are good places to begin, but googling “liquid handling robots” brings up literally pages and pages of, some might say overwhelming, vendor options. When turning to your peers you need to keep in mind that any solution that’s right for them and their application needs may not be the perfect fit for you and your application needs. Get it wrong and you can end up with a very expensive dust collector taking up valuable bench space!

Most likely you won’t get everything on your wish list, but if you actually plan what you need to achieve carefully upfront and then compare each potential solution against your prioritized decision-making criteria, this should be a relatively straight forward process. In this first of two blogs, we’ll start by exploring your motivation for change from manual pipetting to automated liquid handling, followed by how to find the right tool to match your liquid handling requirements and ending with a wrap up discussion about initial versus on-going investment costs.

Why invest in automated liquid handling?

What’s your motivation? Are you looking to increase throughput, miniaturize assays into formats not possible by hand, improve assay reproducibility, reduce the variability of results between scientists, save valuable time, minimize reagent use, save costs, relieve the boredom from the repetitive nature of routine assay preparation, reduce the potential for staff repetitive strain injury, free up resource for other tasks…. all the above and more? There really are a lot of of benefits to be realized but listing based on importance will really help to prioritize your compatibility checklist!

What tasks do you need an automated liquid handler solution to perform?

Does the liquid handling solution need to be versatile, taking the strain in as many applications as possible, or are you looking to fill a niche gap in your liquid handling needs? Are you primarily concerned with dispense performance, so the absolute accuracy and precision of the liquid handling steps is super critical, or do you need it to deliver liquids to extremely precise locations on a plate e.g. when performing serial dilutions in low volumes, or for protein crystallography?

Choosing the right tool for the job

There really are four different classes of automated instrument to consider:

1. Single channel pipettors – highly flexible but slow
2. 96, 384, even 1,536 fixed tip array heads – speedy but lack flexibility, can have washable pin tools or tips
3. 8/16 channel heads with pipette tips – faster than single channel pipettors and more flexible than fixed heads
4. Bulk dispensers – single or multichannel systems – single or multiple reagent dispensers with varying degrees of speed and flexibility

How do you decide which class you should be focussed on? Think about those features required to perform the tasks you identified above? Do you need a pipetting solution for serial dilutions or plate replications (i.e. it aspirates, dispenses and mixes liquids) in which case classes 1-3 will do the job, or a dispenser to deliver bulk reagents, in which case you should be looking at the simple dispensers with low flexibility within class 4? If, however, you are looking for a bulk dispenser that offers more versatility to dispense different volumes of different reagents into different wells at different times, one that eliminates well known assay development bottlenecks and facilitates continuity from assay development into screening, you are not on your own! We heard it too from our customers and developed dragonfly discovery, which arguably splits class 4 in to 4A (limited flexibility) and 4B (versatile) category solutions.

Once you have decided the class, which side of the fence do you sit on with respect to washing non-contact dispense heads versus use of disposable tips? Non-contact fixed heads offer super-fast dispensing, with throughputs that cannot be matched by systems that change tips. They don’t include an ongoing consumable cost but do require routine maintenance to ensure peak performance. On the other hand, disposable tips are a consumable cost to factor in but offer peace of mind with respect to dispense performance, zero system maintenance and the utmost confidence in assay results where any potential for cross contamination needs to be ruled out.

Next topic to consider is about the volume ranges that are used in your lab’s assays. Do you need a small dynamic volume range because you routinely use one microplate format, or a large dynamic volume range to cater for many different microplate formats? Like hand pipettes, robots cater for different volume ranges too, so you need to match accordingly. In my mind automated liquid transfer systems come in 3 classes: classic = >1µL (air or system liquid displacement, sub µL (positive displacement, e.g. SPT Labtech mosquito), sub nL (acoustic and inkjet). Then there are the reagent dispensers that are typically aimed at high speed dispensing in a given volume range band. Often going outside of this band will result in poor dispense performance (if you push to lower volumes than they are comfortable) or a significant speed penalty (if you push them to higher volumes). An exception this is the SPT Labtech dragonfly discovery which covers nL’s to mL’s without significantly compromising dispense speed. What about liquid types, do you ever use any that are viscous or volatile and tricky to pipette? If so, should you be sourcing a positive displacement solution just like your hand pipettes, to continue benefitting from the accuracy of pipetting you have become accustomed to? If working with cells do you foresee any issues with respect to viability post dispensing, or dispenser clogging that requires sanity checking at demo? Do you need to work under sterile conditions? If so check to ensure your proposed solution is small enough to reside in a hood (e.g. SPT Labtech’s dragonfly discovery and Thermo Fisher’s Multidrop^TM) or expect to find significant additional investment. Finally, how about your throughput needs? Should the solution come with a plate stacker (~80 plate capacity), enable integration into a small workcell, or do you just need a standalone solution with a small footprint so as not to take up too much bench space?

OPEX and CAPEX budgets

CAPEX costs are obvious and upfront. Most likely you have a budget defined that needs to be adhered to, unless you come from the “act now ask for forgiveness later” camp! Aside from service contracts (usually in the 10% of purchase price range), OPEX costs can be a little more difficult to calculate and compare. These include use of specialized consumables (e.g. cassettes, liquid sensing tips, plates) which can start mounting up. If you have a rough idea of your throughput, use this to compare OPEX costs across the board.

Check out part 2 where we explore additional points that can catch you out such as microplate format compatibility, acceptable dead volumes and how much time do you want to dedicate to the day to day running of an automated liquid handler? Based on the collective experience of our own sales, support and product management teams we’ve also come up with our definitive check list of considerations which we will share to help guide you to your perfect solution.