Liquid Handling

Analytik Jena offers the perfect liquid handling solution for your daily pipetting routines.

The portfolio ranges from dispensers and automatic simultaneous pipettors to laboratory robots. All liquid handling systems can be tailored to your individual application, throughput and capacity requirements.

Liquid handling

The general term "liquid handling" refers to holding, transporting and dosing liquids during chemical and biological analysis. In labs today, this means liquid handling is one of the key processes that influence the quality of a chemical analysis. Precise, reproducible and efficient handling of liquids ensures that test results meet desired quality requirements and that experiments are consistently reproducible. 

While it used to be the case that manual pipetting was a large part of experimental procedure, today semi- and fully automatic liquid handling systems are increasingly taking over this role. Whether in R&D or industry – modern labs are set up for high throughput in precise analytical procedures. Liquid handling systems enable just this by precisely measuring, transporting and dosing liquids such as samples, reagents and solvents. 

Typical applications of liquid handling include detecting and quantifying nucleic acids (DNA or RNA), the antibody-based ELISA test, or mass analysis of chemical compounds with the MALDI-TOF method. In the biotechnology and pharma industries, in analytic chemistry, in hospitals and diagnostic laboratories as well as in research institutions and universities: Liquid handling is part of the standard kit.

Manual, semi-automatic or fully automatic – An overview of pipetting techniques

Analytic chemistry laboratories work daily with a dizzying array of liquids. They run the gamut from drinking water and surface water, to viscous lubricants, honey, and crude oil. The volume of liquid necessary for each analysis step varies, too, coming in under a microliter in the smallest of samples. Handling liquids in the laboratory is accordingly difficult and has a major influence on the efficiency, productivity and precision of a lab.

Besides traditional manual pipetting, labs have also seen semi-automatic (hybrid) and fully automatic liquid handling stations. The advantage of high-throughput systems lies in the significant time savings, low propensity for error and high cost efficiency that these systems bring. Below, let's dive into the three different liquid handling approaches in detail.

Manual pipetting

Manual pipetting allows the user to precisely dose liquid volumes in the microliter range by hand, depositing them in the desired location. A micropipette is typically used for this purpose. It allows liquids to be manually picked up and then dosed.

These devices differ between single- and multi-channel micropipettes. Single-channel pipettes have one channel and are mainly used in research institutions involved with molecular biology or microbiology, immunology, analytic chemistry or genetics. Multi-channel pipettes have multiple channels, enabling them to pick up and deposit multiple doses of a liquid at the same time, for instance for analyses involving large numbers of samples. Typical applications are ELISA tests, clinical trials, and DNA amplification. 

Pipettes are also distinguished in terms of their function, with some micropipettes utilizing the air displacement principle while others use positive displacement. 

Manual pipetting still plays a major role in liquid handling, but it requires a high degree of care, skill and experience to deliver reliable results in laboratory experiments. It also involves significant labor expense and is not necessarily the appropriate choice for carrying out tests and analyses with a high throughput.

Semi-automatic liquid handling

So-called semi-automatic liquid handling systems are more precise and user-friendly than manual liquid handling devices thanks to partial automation. These are mainly electronic or hybrid systems that a user operates with pushbuttons, preventing user error and increasing dosing accuracy.

A typical example is the semi-automatic pipette, which automates certain basic functions like uptake and dispensing of liquids. The user can set the desired volume on the device and load the liquid with the push of a button. The pipette is then manually positioned over the target and the trigger is pressed again to dispense the liquid.

Automating parts of the liquid handling process that affect precision improves accuracy and reproducibility, although important steps like where the pipette is used, as well as aspiration and dispensing, are still manual. The user also saves time, since it's not necessary to manually set the desired volume, for example. Semi-automatic liquid handling is ideal for labs and institutions with limited budgets and moderate throughput but who still want to automate some parts of the process and increase reproducibility.

Automatic liquid handling

Fully automated liquid handling stations offer the potential to put all liquid transfers in the lab fully in the hands of computer-controlled systems. Automated liquid handling (ALH) is part of the standard complement for modern high-throughput labs, allowing a high volume of maximally precise liquid handling operations under the most stringent quality requirements.

A typical example of automated liquid handling are automatic simultaneous pipettors. These handle parallel pipetting of liquids in hundreds of channels, making them suitable for a wide range of volumes and pipetting heads. High-throughput simultaneous pipettors like these have the potential to drastically increase the productivity and efficiency of large laboratories while meeting the highest requirements for precision, reproducibility and safety. 

Advantages of liquid handling robots compared to manual pipettes

Gradual automation of liquid handling processes has driven a significant increase in lab efficiency and quality since the 1990s. In recent years, liquid handling systems have been continuously improved in order to stay abreast of the increasing demands of modern laboratories. Key advantages of liquid handling robots compared to manual pipettes include:

  • Productivity: Especially with standardized analyses in high-demand laboratories, automated liquid handling has led to a significant increase in productivity. Hundreds or even thousands of time-intensive liquid handling operations can be performed simultaneously, thanks to advanced robot-controlled pipette systems.
  • Precision: Semi- or fully automatic liquid handling stations boast significantly higher precision than manual pipettes. This also makes for much more reliable analytic results at the same time.
  • Reproducibility: ALS stations can reproduce analyses at exactly the same dose, any number of times. Consequently, recurring analyses which require high precision can be reliably carried out, with high inter-sample consistency.
  • Safety: Thanks to robot-controlled ALH systems, laboratory staff remain effectively protected from contact with hazardous or infectious samples. One more advantage: Repetitive steps no longer need to be performed by human hands, thereby reducing the risk of health issues arising from manual pipetting, such as musculoskeletal disorders of the upper extremities.
  • Walk-away time: The "walk-away time" – the time in which the user can leave the analyzer and focus on other tasks – increases with fully automated systems. Cutting-edge machines typically only need to be configured once at the start and, once set up, can run analyses for hours without intervention. At a time when skilled labor is at a premium, this is another important benefit.

Applications and use cases for liquid handling

Handling of liquid samples and reagents is an inescapable part of daily work in a lab. The range of applications for automated liquid handling stations is correspondingly broad. Below are some examples of typical applications:

  • PCR/qPCR: The polymerase chain reaction (PCR) makes it possible to amplify practically any amount of DNA, opening up countless possibilities in molecular biology. Some examples include analyzing minute DNA traces at crime scenes or diagnosing diseases based on a handful of tumor or bacteria cells. The qPCR variant (quantitative/real-time PCR) even allows specific mutations to be tracked in real time. Liquid handling, meanwhile, can drive higher efficiency and reproducibility of PCR tests.
  • ELISA: Liquid handling plays an important role in the ELISA (enzyme-linked immunosorbent assay) technique for detecting proteins, antibodies, peptides, hormones and other molecules. Fully automated liquid handling makes it possible to precisely pipette and mix samples, reagents and other fluids. In ELISA, this precision is particularly critical for dispensing samples, antibodies, and substrates, as well as for cleaning microtiter plates and ensuring uniform mixing of reagents.
  • MALDI-TOF: The mass spectrometry technique known as MALDI-TOF (Matrix Assisted Laser Desorption/Ionization Time-Of-Flight) analyzes molecules like proteins, peptides, nucleic acids and other biomolecules. In this context, automated liquid handling can precisely mix the samples with the matrix and apply the desired dosage to the test plate.

In addition to the example applications mentioned here, there are countless other procedures where fully automated liquid handling offers significant advantages. These include high throughput screening (HTS), used in the pharmaceutical industry to analyze compounds and substances for biological activity. The advantages of liquid handling are also brought to bear in next-generation sequencing (NGS) for cost-effective sequencing of large amounts of DNA.

PCR & qPCR Thermal Cycler

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MALDI-TOF-MS Sample preparation for uHTS

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Trends and outlook for liquid handling

Automated liquid handling systems have forever changed the face of daily work in large laboratories. Great productivity gains have been the result. At the same time, however, developers of liquid handling systems are continuously working to improve the performance and user-friendliness of systems.

For instance, software and ergonomics are increasingly important considerations when acquiring a liquid handling station. Modern systems boast easy, intuitive operation with graphical user interfaces, complemented by visually appealing presentation of results. Labs benefit here by slashing training times and enjoying higher productivity. In this context, modern liquid handling systems are making a foray into artificial intelligence. AI has the potential to shoulder most of the burden of operating liquid handling stations and/or take the headache out of remote-controlling activities.

Another trend has emerged in recent years is miniaturization of workstations. Pipetting platforms for automated liquid handling are being built with increasingly slim form factors, saving valuable lab space. Meanwhile, average liquid volumes processed by liquid handling stations are declining. Modern machines are already leveraging contactless dosing methods which allow precise dispensing of liquid volumes in the sub-microliter range. This is a trend that will continue in the future.