Liquid Handling Machines: What It Is and Its Value

Liquid handling machine

Liquid handling machines are robotics that can automate pipetting works in a wet lab. Though robotics can be efficient, many misunderstand what exactly they do. This article explains the features of liquid handling robotics, some misunderstandings people have, and the main benefit the robotics can bring. Hopefully, this article can help you understand what liquid handling machine enables.

What is a liquid handling machine?

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In short, a liquid handling robot is a workbench with robotic arms that automate wet-lab workflows by running pre-configured scripts.

Workbench

Workbench is a place where labwares and tools are placed. The tools placed onto a workbench define the workflows the machine can enable. Some manufacturers allow tools too large to fit into a workbench to be placed around the workbench. Below is a list of labware and tools that can either be placed within or integrated with a liquid handling machine.

Labware typically placed on the workbench.

  • standard plates like 96 well plates
  • tubes supported by tube racks.
  • troughs that store reagents
  • pipette tips

Tools typically placed on a liquid handler

  • heater/ cooler
  • shaker
  • thermal cycler
  • magnetic station
  • plate storage station

non-typical tools placed on and around liquid handlers

  • spectrophotometer
  • barcode reader
  • centrifuge
  • freezer/ refrigerator storage
  • HEPA filter
  • weight scale
  • colony picker

An operator typically prepares a run by loading the worktable with labware, such as tips and plates, and subsequently fills the troughs with reagents and buffers before initiating the workflow.

Robotic arm

A typical liquid handler can come with three types of arms. Arms of your choice can be chosen based on your needs. The maximum number of arms is usually three, and some robots have multiple of the same arm.

The most popular arm is the 8-channel pipetting arm. The popularity comes from its flexibility. Not only can the arm aspirate and dispense in unison, but the channels can also move independently. This arm allows common pipetting technique done by human, using either a single-channel pipette or an 8-channel pipette.

The next most used arm is the robotic gripper arm. This arm can move labwares around. This arm allows for movements of labware across different tools, instead of simple dispensing on the same spot.

The final arm type is the 96/384-channel pipetting arm, capable of dispensing liquid in 96/384 tips simultaneously with a single pipetting motion. This arm allows for speedy processing of samples, which increases turn-around time. Another benefit is in its ability to dispense reagents without without time delay, a crucial factor in spectrophotometric experiments.

The script

Liquid handlers operate based on scripts entered into their software. Typically, lab managers will discuss the workflows they want to automate with an engineer at the manufacturer, and the engineer will create the automation script. The software allows for flexible workflow by accomodating variable inputs and if-else statements.

For example, a script can allow users to input the volume of the dispensed liquid for each wells, and the number of plates the user needs to process before the run starts. With these information, the robot can calcualte and inform the operator of the volume of reagent needed. Once the run begins, the software can instruct the robot to use back-up storage positions only if the number of plates is too high to be handled on the worktable alone.

People’s misunderstandings about liquid handling robotics

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Though liquid handlers can be efficient, many misunderstand the capabilities of the robots, thus have inappropriate expectations. Here, I outline some of people’s most common misunderstandings.

Ability to automate a workflow end to end.

When considering a liquid handler, people usually want to automate the complete workflow from the reagent input to the final plates. However, whether end to end automation can be achieved depends on the length of the workflow and the size of the workbench.

The length of the hands-free workflow is directly proportional to the size of the workbench. A short workflow that only uses a few labware can often fit every labware onto the workbench, thus possible of end to end automation. However, a long workflow that requires many labware, usually tips, needs to be divided into several steps, so that necessary labware can be replenished.

There is a trade-off relationship between the length of the automated workflow and the size of the robot. The challenging factor for people to decide upon is that the size of the robot is typically proportional to its price.

Ability of the robotic arm

A robot by its nature is usually not as flexible as a human. The liquid handler robotic arm can move in x, y, and z directions. However, it does not have the flexibility of performing twisting and twirling movement. For example, If you have a workflow where you need to hold the pipette in a slanted position, the robotic arm may not be able to do it. Some manufactureres may have workaround tools that let the labware sit in a slanted position, or other clever tools that make up for the inflexibilities, but do not expect the robot to have human dexterity.

Also, the reach of the robot’s arm is usually a lot more limited than a human’s arm. The robot arms usually sit on a rail in a sequence, so the arm on the far end cannot reach the other end of the table. The liquid handling engineer usually designs the worktable with these limitations in mind, so a user may not need to overthink. However, the worktable space that each arm can fully utilize is often more restricted than many imagine.

The liquid handler arm is not as flexible as the human arm, but clever designs and workarounds may alleviate the issue. If your workflow involves special pipetting maneuver, an engineer may be able to help you through a consultation.

The speed of sample processing.

Many expect the robot to work faster than a human. However, the speed of the robot is actually similar to that of a human operator. The 8-channel arm and the gripper arm still need to perform the same tasks as a human, albeit less flexibly. Though a liquid handler is uniquely capable of dispensing with a 96/384 channel arm, the decrease in workflow time is usually marginal, because the 96/384 arm is not as frequently utilized as the other arms.

Do not expect the robot to significantly improve the turnaround time, as the speed of sample processing is usually comparable between humans and robots. The benefits of liquid handling robotics lie elsewhere.

The main benefits of liquid handling robotics

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There are three main benefits to utilizing liquid handling robotics.

Walk-away time

Labs typically employ many clever, highly educated researchers to perform experiments, but the majority of the experimental work is usually repetitive pipetting tasks. Introduction of liquid handling robotics frees up pipetting responsibilities and allows scientists to focus on science.

Consistency


Liquid handling robotics deliver consistent results, and this consistency is replicable across robots. Unlike human operators, who may vary in consistency from person to person, day to day, or even before and after lunch, the robots and their scripts can consistently deliver replicable results. In case of scaling, another robot can be bought with the same configuration and script without worrying about the variability between different workers. These factors combined leads to more reliable experimental outcomes.

Reduced human management

When hiring a human worker, there are many risks and considerations that need to be taken into account, which implementing liquid handling robotics does not require. For example, the experimental workflow needs to be taught for a few months whenever a new operator joins. There is a risk of the operator quitting. Having more staff also puts a burden on the lab manager. Implementing a robot frees up these problems.

Of course, robots have its own set of risks and considerations unique to robots, like error handling and maintenance. It is up to the lab managers to decide whether the benefits outweighs the cost.

Conclusion


Here, I have outlined the capabilities of liquid handling robotic, the misunderstandings people often have, and the main benefits it can bring. The liquid handling robot can automate the wet-lab workflow of a lab through the use of its workbench space, arms, and automation script. However, the liquid handler may not completely automate your workflow, is usually not as flexible as a human, and is not faster than a human. The main benefits of implementing a liquid handling robot lie in the increased walkaway time, improved consistency, and reduced human management. I hope this article has helped you in your consideration.