What are Liquid Handlers?
Learning Objectives
- Define what a liquid handler is and what it is used for
- Discover the history of liquid handlers and their development
- List the advantages and disadvantages of using a liquid handler
- Evaluate future applications of liquid-handling technology
What are liquid handlers? The history and future of liquid-handling technologies for efficient scientific and high-throughput discoveries.
Legend
Shown above is an image that reads the question “What are liquid handlers” and “The history and future of liquid-handling technologies for efficient scientific and high-throughput discoveries.” To the left is the Brand LHS Liquid Handling Station with robotics capable of pipetting small volumes of liquid throughout the station. To the right is the ErgoOne Multichannel Pipettes, which is a handheld device capable of transporting eight volumes of liquid within a plate. An arrow is drawn between the two images to show movement from more low-throughput to more high-throughput technology. Image created using Google Slides and image credits described in sources.
Introduction
Innovation and discovery has been a model of the exploration of science and technology throughout history. A hallmark of the human experience is this passion and curiosity that leads to exciting and powerful developments in science. Improvements in early medicine, such as early nasal reconstructions performed using a cheek or forehead flap as replacement for the tissue to plastic surgery as we know it today, have been critical to the development of patient treatments and research (3). As science has continued to progress, there is a newfound emphasis on efficiency to discover methods that led to scientific discovery at an accelerated rate. One such example of this is the development and improvement of liquid handlers. This technology was developed in response to the growing need in biotechnology to perform experiments with increasingly smaller quantities of liquid as a means to reliably collect these small samples with some increased efficiency. With the use of a liquid handler, researchers have opened the door to a breadth of opportunities to develop scientific discoveries more effectively.
Background
Prior to the invention of liquid handlers, small liquid volumes were distributed utilizing a “piston-driven, plastic-tip micropipette” created in the late 1950s by Heinrich Schnitger. This was an improved successor to the Carlsberg pipette, which was made by pulling at one end of a glass tube that was heated over a Bunsen burner to create a capillary, which relied heavily on the expertise of the user and the variable construction of the pipette (4). This was an unreliable system, and the introduction of Schnitger’s micropipettes presented necessary technological and safety improvements to the Carlsberg pipette. The introduction of automated liquid handling began in the 1970s, where liquid handling automation systems were created by adding a motor to a pipetting device, however, there was no means to control the motor, meaning it was not popularized in the scientific community (5). In the 1980s, the development of electronic elements and components led to the automations of liquid handlers to perform complex protocols (5). Throughout the years, liquid handling has continued to adapt to the growing scientific needs of today, particularly coinciding with the growth of high-throughput screening, leading to the mainstream adaptation of liquid handlers and a transition to generating handlers that were capable of performing complete experimental tasks rather than just the precise volume transfer. Today, liquid handlers can be used by researchers for a variety of tasks that make experimental protocols more efficient for their discovery.
Advantages and Disadvantages
It had been discussed that liquid handling makes scientific discovery more efficient, but there are a multitude of advantages that make these resources a fantastic tool for researchers. Aside from being tools that are capable of dispensing liquid much more efficiently than doing so individually, liquid handlers are also increasingly more precise. Particularly when considering robotic workstations that involve liquid handlers, there is an immense advantage in the consistency and accuracy of relying on a machine over humans, who are naturally prone to error (6). Additionally, humans experience fatigue and will lose precision where a machine cannot. Another benefit towards the use of liquid handlers is their capability to increase the reproducibility of an experiment. Due to the reliability of the handlers, there is an increased trust of the validity of such experiments, and there is the additional benefit of having a simple means to set up the experiment for additional runs (i.e., applying the same programming to the handler for additional testing). While there are a multitude of advantages to the use of liquid handlers, there are a few notable disadvantages. One pressing example is the cost of liquid-handling technologies, as they are a significant investment in a laboratory budget. Typically, the price of a liquid-handling workstation will vary between $50,000-$250,000 (7). Additionally, there is no capacity for independent troubleshooting capability when using independent handlers. With a human user, one may notice a problem within the experiment and be able to adjust, while the liquid handler operates on programming and does not have this ability to quickly adapt. Liquid handlers, although efficiently automated, do continue to require a person to set up reagents and experimental materials, in addition to setting up the program necessary to run the machine.
Liquid Handling in the Future
With all of the advantages of liquid handlers and their various applications, it is important to consider where improvements can be made to continue to further scientific discovery. For better efficiency in genomics laboratories with liquid handlers, one might consider new adaptations for evaporation control. This is because long automated protocols that lack input from the user beyond set up are limited by the uncertainty of such small liquid volumes resisting evaporation (7). One may also consider the adaptation of artificial intelligence, perhaps to address the lack of independent adjustments, and to utilize machine learning to increase adaptability (5). Throughout history, the growth and improvements made to liquid handlers can be followed with increased technological advancements. Their increase of efficiency and reliability has led to many laboratories exploring liquid-handling techniques and introducing these resources to their repertoire. While the cost of liquid handlers may be high, the benefit of having the ease of experimentation can outweigh the necessary initial investments.
Questions and answers
- What are liquid handlers?
- Liquid handlers are devices utilized to handle and disperse small volumes of liquid, ranging from low-throughput handlers to high-throughput automated handlers to distribute high quantities of liquid simultaneously. They are utilized in a variety of fields, including microbiology, synthetic biology, genetics, etc.
- Why are liquid handlers important?
- Liquid handlers are vital to the scientific process and continue to develop discoveries as they increase efficiency and reliability of experiments across several branches of science. This is crucial as scientific discovery requires replication to provide evidence to support a hypothesis correctly.
- List one advantage and one disadvantage of liquid handlers.
- One advantage of liquid handlers is that it eliminates the possibility of human fatigue causing problems in an experiment. One disadvantage of liquid handlers is that they are a large initial investment, so laboratories must consider if having a liquid handler would be helpful to their workflow.
- Consider the potential future applications of liquid-handling. Where do you see gaps in the technology to address?
- One gap in liquid handling is that it is not well-equipped for more viscous materials and leads to a gap in liquid-handling technologies. Future research may consider addressing this gap, or considering other future contenders, such as the development of appropriate artificial intelligence.
- Why might someone not choose to use a liquid handler?
- Someone may not want to use a liquid handler if the cost is too high for their laboratory to manage and justify. Additionally, if the researcher is pipetting many different solutions, doing so may be better and quicker by hand.
Audio Recordings
References
Liquid handling station (LHS). (n.d.). Retrieved February 25, 2022, from https://brandtech.com/product/liquid-handling-station/
ErgoOne® Multichannel pipette. (n.d.). Retrieved February 25, 2022, from https://www.usascientific.com/ergoone-multichannel-pipette/p/ErgoOne-Multi-Channel
Shaye, D. A. (2021). The history of nasal reconstruction. Current opinion in otolaryngology & head and neck surgery, 29(4), 259.
Klingenberg, M. (2005). When a common problem meets an ingenious mind: the invention of the modern micropipette. EMBO reports, 6(9), 797-800.
Automated Liquid Handling Evolution: An overview. (2019, November 05). Retrieved February 25, 2022, from https://perkinelmer-appliedgenomics.com/2019/07/29/automated-liquid-handling-evolution-an-overview/
Kong, F., Yuan, L., Zheng, Y. F., & Chen, W. (2012). Automatic liquid handling for life science: a critical review of the current state of the art. Journal of laboratory automation, 17(3), 169-185.
Tegally, H., San, J. E., Giandhari, J., & de Oliveira, T. (2020). Unlocking the efficiency of genomics laboratories with robotic liquid-handling. BMC genomics, 21(1), 1-15.