Introduction
In today’s world, laboratories are under pressure to maximise efficiency (throughput), provide rapid result delivery and meet research goal milestones, while at the same time minimise errors and rework. This is typically achieved through substantial pressure on human resources, with the primary goal of maximising company profit.
Laboratory automation, digitisation of lab process, and seamless integration of these technologies (often referred to industry 4.0) are now widely used in certain chemical industries, such as pharma and drug discovery laboratories. However, these advancements have yet to be broadly adopted in chemical research laboratories, despite some very good efforts by an increasing dedicated community at the university of Liverpool and elsewhere.
Laboratory automation has transformed the way technicians and researchers handle sample preparation, providing enhanced precision, efficiency, and reproducibility. This automation is particularly beneficial for sample preparation tasks that are often time consuming and repetitive such as pipetting, diluting and mixing.
The main types of laboratory automation are:
- The movement and organisation of samples within the laboratory, typically achieved using conveyer belts or robotic arms.
- The automation of measurements, exemplified by instruments such as automatic titrators.
- The synthesis of molecules, which involves controlled addition of reagents to produce specific molecules, usually with the ability to measure success or otherwise through simple spectroscopic monitoring.
- The automation of sample preparation methods ready for analytical measurement, including the use of sample automation rails and pipetting robots.
This article explores the key aspects of automation in the context of analytical testing, with a specific focus on sample preparation aspects. It compares various commercial systems, highlighting their benefits and limitations. There are many more automation systems than those reviewed in this article - this is more a user’s perspective review.
Benefits of laboratory automation
Automating processes in the laboratory has numerous benefits in higher throughput, redeployment of critical human resource, improvements in reproducibility, lowering on-going costs and benefits to both the environment and human health.
Redeployment of critical resources
This is by far the most important benefit for the laboratory. Automating sample preparation allows scientists to focus on other critical tasks, such as data analysis, leading to more time to analyse data and make better research decisions. This speeds up the research process and gives laboratories a competitive edge. In addition, as robots don’t need sleep or require breaks, automated systems can prepare samples overnight or even over the weekend, ready for analysis upon the scientist’s return.
Precision of data and sample preparation steps
Robots and automated systems ensure tasks are performed consistently, increasing the precision of the data and the sample preparation processes. For example, below is an example of the precision of delivering a small volume to a vial. This data is part of a validation exercise for a Gerstel automation rail. The volume is very small, but it still delivers with excellent precision. The %RSD is smaller than most pipettes.
Reproducibility of data
Automation improves the reproducibility of data and processes by eliminating the variations between technicians and any environmental factors, increasing confidence in results, and reducing measurement uncertainty.
Downsizing of sample preparation methods
Most sample preparation methods that are automated require miniaturisation, which is typically dictated by the size of the vials used. While this is a necessity, it also offers additional benefits, such as reducing the amount of solvents and reagents needed. Consequently, that method becomes more environmentally friendly, cost effective and generates less waste. Furthermore, it minimises exposure to harmful chemicals, thereby enhancing health and safety.
Reduction in manual handling
Many sample preparation methods are long, containing many steps. Some of these steps are repetitive and can be hard on the body, for example shaking. Automation eliminates these steps for the technician, greatly reducing the chance of injury through repetitive movements.
Sample preparation using automation rails
Automation rails, such as the ones produced by PAL and Gerstel, are specialised systems designed to streamline and automate various aspects of sample preparation in laboratories. These rails can be configured as stand alone units (offline) or integrated directly with analytical instruments (online), allowing for seamless sample preparation and injection.
The components of an automation rail typically include robotic arms, which are used for liquid transfer and vial transportation, and various modules for tasks such as pipetting, diluting and mixing. The software used to control these systems has been designed to be technician friendly, although some are easier to use than others.
PAL systems
PAL automation rails are manufactured in Switzerland and are the most widely used and successful automated sample preparation and handling platform (Fig. 1).
The sample preparation options on these rails are:
- Derivatisation
- Incubation
- Centrifugation
- Dilution and standard addition
- Vortex mixing
- Temperature controlled storage
- Transport of vials (by use of magnetic caps)
- Automatic robotic tool change (in the case of multiple volume dispensing)
- Barcode reader
These automation rails can also do:
- Liquid / liquid phase extraction
- Liquid / solid phase extraction
- Micro solid phase extraction (SPE)
- Static and dynamic headspace
The PAL rails can be connected to instruments and have the following injection techniques:
- GC liquid
- LC liquid
- Headspace
The PAL automated rails use PAL Method Composer software to allow sample preparation methods to be written, which are a list of commands for the steps you need for your sample preparation.
This software is not as user friendly as some but has the advantage of permitting more than one sample preparation step at once (parallel mode), which is an advantage over some of the competitors who have hard wired protections in place that force the rail to operate in a sequential mode only.
The rails have both offline (only sample preparation) and online options (sample preparation and injection into an analytical instrument).
Gerstel systems
Gerstel is a German company that specialises in sample automation rails and components. The rails contain most of the components the PAL rails have but Gerstel have a few extra components that PAL do not produce. These rails also can be a stand-alone rail (offline) or can be attached to instruments (online) allowing sample preparation followed by injection into an instrument.
Because of the extra components available, these rails are very good for long, complex sample preparation methods. The rails can be up to 2 meters long and can fit many sample preparation components.
The software used for Gerstel rails is Maestro. This software is very easy to use, no coding is involved, just an easy set of commands to complete sample preparation. The only limitation of the software is that only one task can be performed at once, lengthening the total time of the sample preparation.
The following is a list of some of Gerstel’s specialised components (see Fig. 2):
- Filtering station. This allows automated filtration of samples to remove unwanted particles from your samples.
- Sample evaporation station (m-VAP). Allows six samples to be evaporated in parallel. Evaporation is accelerated by lowering the pressure down to vacuum and by heating and mixing the samples.
- Ultrasonic water bath. This holds six samples at a time and is a very useful tool to help dissolve samples while heating.
- Analytical balance. A balance can be fitted to the MPS system and can communicate with the maestro software to automatically add weights into the software.
- The Twister is the SBSE (Stir Bar Sorptive Extraction) solution from GERSTEL. It enables analytes from liquid or gaseous samples to be enriched solvent-free. Due to the large phase volume, the Twister is very sensitive and is therefore especially suitable when performing trace analytics.
- TP-SPME (Thin-filmed-solid-phase-micro-extraction). The adsorbent has been applied to a rectangular film. For enrichment, the film with the adsorbent is either suspended directly in a liquid sample or in the headspace above the sample. The analytes accumulate on the adsorbent.
Vial sizes and transport of vials around the rail
Both the PAL and Gerstel systems can use vials ranging from 1.0 mL to 20 mL. Vial sizes greater than 20 mL will not fit some stations on the rail. Adapters are used to accommodate different vial sizes in the stations.
Vials are moved between stations via magnetic caps on the vials. In the robotic arms there are tools that have magnetic bottoms. These pick up a vial and move it to a new location. The magnet is released as the robotic arm moves sideways.
Limitations of automation rails
- Most sample preparation stations can only hold 6 vials at a time. Large sample numbers require sample preparation in batches of 6, lengthening sample prep time.
- The PAL Method Composer software is hard to use in comparison to the Maestro software on the Gerstel rails.
- Although method miniaturisation has many benefits, some sample preparation methods cannot be downsized.
- The Gerstel software doesn’t allow multitasking of sample preparation steps as it is a linear process.
Sample preparation using pipetting robots
WATERS Andrew+ pipetting robot
The Andrew+ pipetting robot provides fully automated liquid handling using electronic pipettes and labware holders called dominos. This flexible system allows you to easily switch from tedious manual pipetting to error-free, fully automated lab workflows, without needing any programming, laboratory robotics, or automation engineering knowledge. The Andrew+ uses single and multichannel pipettes, which are specially designed and manufactured by Sartorius for the Andrew+ robot.
This provides superior experiment reproducibility, pipetting speed, and a market leading dynamic range of dispensing volumes for a liquid handing robot –from 0.2 µL up to 10 mL.
There is a wide range of dominos, catering for all sizes and shapes of vials. The dominos are magnetically bound and can be rearranged easily. The dominos are set into 2 rows making the system very compact, easy to fit into most laboratories and even into fume hoods when working with dangerous chemicals or solvents.
As with the automation rails, the Andrew+ eliminates most human errors resulting in more reliable data and improved reproducibility. Normal pipetting requires repetitive movements which can cause repetitive strain injuries but the Andrew+ eliminates this exposure.
The dominos also have heating and shaking options and can perform solid phase extractions (SPE). Laboratories commonly use the Andrew+ for PCR prep and plasmid DNA prep.
Application notes are supplied for methods developed on the system which gives many laboratories a starting point for their sample preparation methods.
The software is One Lab which is very simple to use. The software allows scientists to graphically design their pipetting protocols in minutes, even allowing for remote monitoring of the system.
The Andrew+ is one of many pipetting robots on the market but seems to be widely used and has a good reputation.
The limitation with the pipetting robots is that they can only do basic sample preparation methods. For example, centrifugation or evaporation require an automation rail.
Mobile automation robots
The University of Liverpool have developed a robot scientist, which is an intelligent system that uses AI and a flexible arm with customised gripper, that can conduct experiments by itself. They refer to the robot as a new lab assistant with a strong work ethic. The robot is 1.75 m tall which can move around the laboratory, avoiding co-workers and obstacles. This is done using a combination of laser scanning coupled with touch feedback for positioning, rather than a vision system. The robot moves to different workstations in the lab and can perform a wide range of sample preparation tasks independently.
The robot can work for 21.5 hours a day, seven days a week, with the robot stopping only for battery changes or maintenance. It can carry out the following tasks:
- Weighing of solids
- Dispensing liquids
- Removing air from vessels
- Running catalytic reactions
- Quantifying reaction products
By working around the clock, the robot can speed up scientific discovery by tackling large and complex problems that are currently too time consuming for humans to perform. It also allows scientists to think creatively.
Building an AI logic for the robots is a game changer. The robot can process analytical datasets to make an autonomous decision. For example, if the robot had finished a reaction and needed to know what reaction to complete next or carry on with the current reaction, the robot will decide basically instantaneously after scanning analytical databases and then move on. This same review process by a chemist could take hours.
Limitations of automated systems
One of the primary challenges with automation is the large initial investment required to purchase the system, which can be prohibitive for small laboratories with limited funds. Additionally, most components on the automation rails have a set number of vials that they can accommodate and sometimes the vial sizes are fixed for these components. This can make it difficult to use different vial sizes throughout a sample preparation method. While most components can take different vial sizes by using inserts, these are fixed for the entire run. For example, if a centrifuge is set up to take 10 mL vials, no other vial sizes can be centrifuged during that run. Another limitation is that some systems can only perform one task at a time. Furthermore, consumables such as vials and caps can be expensive, so it is beneficial to search for alternatives to the vendor’s branded consumables.
Conclusions
Even with the initial large investment, automated sample preparation systems are an excellent addition to a laboratory, where the benefits can clearly outweigh the limitations. Together with a strong laboratory information management system (LIMS) where data can be interfaced it is possible to dramatically improve efficiency in the laboratory. For a routine analytical laboratory, a mixture of sample preparation rails and pipetting robots would be most beneficial, although it depends on the complexity of the methods.
The future of automation in laboratories is moving robots and the use of AI and machine learning to further speed up sample preparation and research. Once these robots become cheaper and more accessible, more laboratories will look at this technology.
Automation systems are invaluable tools that enhance the efficiency and accuracy of laboratories. However, the dedication and expertise of scientists remain essential for researching innovative ideas, understanding and analysing data, and troubleshooting complex issues.
Bibliography and further reading
- 21/01/2025 https://www.sciencedirect.com/science/article/pii/S247263032201706X
- 21/01/2025 https://www.palsystem.com/en/
- 23/01/2025 https://www.andrewalliance.com/
- 14/01/2025 https://www.andrewalliance.com/case-studies/five-golden-advantages-of-liquid-handling-automation-when-applied-to-metabolomics-research/
- 14/01/2025 https://www.andrewalliance.com/case-studies/researchers-at-bayer-successfully-automate-the-preparation-of-oligonucleotide-loaded-lipid-nanoparticles-using-the-andrew-pipetting-robot/
- 16/01/2025 https://www.andrewalliance.com/case-studies/working-with-liquid-handling-automation-from-outside-the-lab-to-maintain-productivity/
- 16/01/2025 https://www.weforum.org/stories/2020/08/robot-scientist-experiments-covid-19-lockdown/
- 23/01/2025https://www.liverpool.ac.uk/science-and-engineering/news/articles/ai-driven-mobile-robots-team-up-to-tackle-chemical-synthesis/
- 23/01 /2025https://www.theengineer.co.uk/content/news/liverpool-researchers-build-mobile-robot-scientist/
- 23/01/2025 https://gerstel.com/en/products
- 23/01/2025 https://www.the-scientist.com/the-latest-in-lab-automation-71462
