Liquid Handler Design for High-Density Plate Formats

The push to higher density plate formats in biopharma research has been underway for quite some time, as it is seen as a principle means of reducing the costs of experimentation through higher unit throughput per time slice, and lower reagent volumes per data point. While automated liquid handling technology widely handles 96-well plates with ease, progressing to 384 or 1536 well plates has posed challenges in terms of accuracy and repeatability of head/tip alignment as the higher density plate wells are much smaller and accordingly less forgiving.

Liquid handler nest

While core instrument alignment, use of robust components, and high accuracy gantry robots all help an automated liquid handler perform better with high density plate formats, nest design is arguably one of the most important elements to consider if you are planning on buying an automated liquid handler with high density plates in mind. This is because even with high quality and precise robotics and components, there is typically room for location variation between a plate and a standard nest in excess of what can be reasonably tolerated for accuracy and repeatability in a 384 or 1536 plate.

The problem of plate to nest location is not hard to overcome, and can be done with mechanical locating elements that force the location of the plate within the nest to a fixed position each time. This locating feature thus reduces the plate to nest location error margin, greatly increasing the ability to repeatably process high density plates.

Many liquid handlers offer this type of nest location, as a per nest option. That is, when purchasing a liquid handler, you can decide to add locating mechanics to some number of nests, at an additional cost. However, the result is typically a deck with some locating and some non-locating nests, which results in constraints on how protocols are designed and often how much throughput is possible. If you have an 84 position deck with only two locating nests, you effectively have a 2 position liquid handler if you are targeting 1536 plates.

By contrast, all 10 of the dynamic nests on Prime come with plate location as a standard feature. Because Prime has the ability to load labware on one dynamic tray while aspirating and dispensing on the other, creating the continuous pipetting benefit, the 10 locating nests actually perform like a nearly limitless nest supply – you will almost never be waiting on nest availability if you can load and unload in parallel to core liquid handling functions.

So, if your plans include high density plate formats, it is important to give real consideration to the number and configuration of locating nests on your deck

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