Imagine a woodcutter chopping down a tree with a blunt saw, being too busy to sharpen it. Today ‘’sharpening the saw’’ means ensuring we have the right tools and technology to be more productive and efficient. When it comes to laboratories all around the world, this principle is firmly associated with liquid handling systems. Especially novel automated technologies are becoming a great tool today and a necessity in health and life science laboratories to keep up with the demand for efficiency, accuracy, and high throughput.
In this article, we will provide an overview of liquid handling systems, focusing on automated liquid handling systems with benefits, challenges, solutions, and the future of the systems.
What are liquid handling systems?
In general, liquid handling means transferring liquids from one container to another. This can be done manually, semi-automatically (‘’hybrids’’), or fully-automatically with automated liquid handling systems (ALH systems). Types of liquid handling systems include pipettes and micropipettes, both analog and electronic, with fixed and disposable tips, washers, microtiter plate reagent dispensers, stackers, handlers, burettes, software, reagents and consumables, and some other products. There is a broad volume range from liter down to picoliter levels. Also, femtoliter pipettes can be found on the market, which usually utilize surface tension and air pressure control. There are options spanning from small, simple pipettes to full-scale, multifunctional automated workstations.
Liquid handling is an extremely important practice in all biotechnology and pharmaceutical industries, research institutes, hospital and diagnostic laboratories, academic institutions, and others. There are many applications for laboratories to use the systems – drug discovery, genomics, clinical diagnostics, proteomics, and many other fields.
A rapid increase in assays being performed for various research purposes, such as target screening, has increased the demand for low-volume, high-throughput liquid handling technologies. ALH systems have become essential in workflow in most large- and medium-scale life sciences research laboratories worldwide.
Figure 1: History of liquid handling systems (Source: Industry Journals, Investor Presentations, Primary interviews, Grand View Research)
Current state and outlook of liquid handling systems
The market in this area is showing no sign of slowing down. Quite the contrary! Fundamentally, the market is driven by the global expansion of pharmaceutical and biotechnology industries, especially the R&D sector, the growth of life science research, favorable funding scenarios in all sectors, and many other reasons. The COVID-19 pandemic additionally boosted the growth of the market.
Also, developing regions like Asian-Pacific and Latin American regions are rapidly improving life science research infrastructure and are the fastest growing markets of liquid handling systems. However, the U.S. still holds the largest market share. This market may even be boosted by the Executive Order on Advancing Biotechnology and Biomanufacturing Innovation, signed on September 12, 2022.
Manual liquid handling systems
Manual liquid handling technologies are still the basis in all the laboratories around the world, especially pipettes, due to their easy-to-use feature and range of applications – a wide variety of experimental processes and analysis in molecular biology, biotechnology, chemistry, etc. Therefore, the pipette market is expected to continue dominating the market.
Manual products are pipettes, which can be disposable (used for rough measurements only) or transferable, single- or multi-channel (most common configurations of channels are 4, 8, 12, and 98), and dispensers which allow dispensing specific volumes into multiple receptacles without aspiration in between. Drawbacks are the low throughput of samples involved, not that great reproducibility, high labor cost, and the chance of repetitive stress injuries.
However, over the years, manual liquid handling technologies have become more accurate, precise, safer, and more comfortable to use.
Figure 2: Manual pipettes (Source: Gilson)
Semi-automated liquid handling systems
Currently, some manufacturers are focusing on semi-automated (electronic or hybrid) systems to bring some level of automation to labs with limited budgets that don’t permit start-to-finish automation. Such systems usually operate through push buttons, thus offering a higher level of easy-to-use and flexibility than manual pipettes. This type of system allows researchers to leverage novel systems and technologies alongside one another to automate specific parts of the workflow. These types of systems allow moderate throughput and higher reproducibility with less labor costs.
Figure 3: Semi-automated pipettes (Source: Integra)
Some significant manufacturers of manual and
semi-automated pipettes are:
- Eppendorf
- Gilson
- Hamilton Company
- Integra
- Mettler Toledo
- Sartorius
- Thermo Fischer Scientific
At BioSistemika, we have also developed a semi-automated liquid handling product PlatR – an easy-to-use tablet application that guides you through microplate while pipetting by illuminating the correct wells. It is a perfect solution to minimize common errors during pipetting and can lead to discarding costly reagents and materials. It is also a great way to make the first step towards automation.
Figure 4: PlatR – hybrid liquid handling system
Automated liquid handling (ALH) systems
An automated liquid handling system is a device that performs liquid transfers via computerized systems. One major part is software that enables users to perform different protocols on the system. These devices offer precision sample preparation for high-throughput sequencing or screening, liquid or powder weighting, bioassays of many kinds, etc. There may also be heating/cooling and shaking or centrifugal components built in (e.g., C.WASH by Cytena – plate washer that uses centrifugal force to remove liquids from well plates contact-less).
Some are even physically constructed for easy integration with peripheral labware using robotic arms. Those are especially common in medium- and large-sized life science companies that perform a lot of R&D.
Some major manufacturers of automated liquid handling systems are:
- Agilent Technologies
- Analytik Jena
- Aurora Biomed
- Autogen
- Biotek Instruments
- Corning
- Eppendorf
- Gilson
- Hamilton
- Mettler Toledo
- Opentrons
- Tecan
- Thermo Fischer Scientific
Figure 5: Automated liquid handlig system (Source: Analytik Jena)
Benefits
Particularly in large companies, there is a huge demand for automated systems. Utilizing automated systems can take human variables out of pipetting and offer more repeatability and precision, minimizing errors, and variability, improving records and tracking, increasing throughput and reproducibility, conserving agents, and reducing hands-on time. The latter is important to reduce the workload of researchers and operators, allowing them to focus on more valuable contributions to the work instead of manual tasks. With automatization, there is also more protection from hazardous and infectious samples.
Also, stress injuries, like carpal tunnel syndrome, tendonitis, etc., are common when people perform repetitive liquid handling tasks; therefore, with automatization, companies introduce additional long-term health and safety measures in their workplace. Overall, automated liquid handling systems can save a lot of money and time and protect the well-being of employees.
Challenges & costs
However, there can be some challenges here. Incorporating additional electric components improved the technology and allowed the instrument to be more reliable, precise, faster, and efficient. On the other hand, many different internal actions must work within specifications. Otherwise, errors can happen. Those can be expensive in terms of the process halt.
There can be complex operability of advanced systems that need skilled professionals to operate with them. That can be a problem, especially in developing countries lacking infrastructure and qualified personnel.
One important aspect is price. With the addition of calibration and maintenance costs, the high cost of advanced automated workstations is expected to limit adoption in small and medium-scale companies. A small, automated robot system can cost in the $100K to $300K range, whereas larger, more complex systems can quickly go into the $1M or greater range. In addition to capital and integration costs, there could be changes to building infrastructure, as well as maintenance and calibrations can be quite expensive, lab staff technical training, and maybe hiring your own automation engineer.
Bringing in new tools and technology can still be a daunting process, especially for small and medium-scale companies. Besides the investment aspect, the major inhibiting factor is the fear that automation might make day-to-day activity more challenging. Primarily because of the perceived need for extensive upfront training and reliance on dedicated experts to handle systems on an ongoing basis. Therefore, they rather invest in employees performing the work ‘’old-fashioned’’ way.
Companies that have liquid handlers with more intuitive software have an important competitive advantage.
Emerging trends
Many manufacturers are beginning to focus on providing intuitive software alongside the systems, with an approachable graphical user interface that is quick to learn and easy to use. Many recent products in this market are bucking that trend to put software at the forefront of the user experience. This also shifts the reliance on the instrument vendor experts for new protocols.
One important aspect of this market is also the miniaturization of the systems. Small benchtop workstations reduce workflow expenditures, decreasing the use of expensive reagents and materials.
Lately, artificial intelligence is making its way into the market. Some companies are using AI to identify and solve problems within the system. AI will also be used to learn protocols and assist in different stages of the process so that the instrument can be controlled remotely.
Another emerging trend is cloud-based peer-to-peer sharing of the protocols. Currently, some restrictions with current software don’t enable transfer protocols between systems with different configurations. Vendors enabling peer-to-peer sharing of expertise easily transferable between the systems will likely gain adoption.
The future of the market
Due to decreasing liquid volumes (better efficiency throughput), the introduction of novel methods of automated liquid handling workstations is anticipated to drive the market, especially non-contact dispensing. It can operate with picolitre volumes, and in addition, it prevents cross-contamination. To overcome surface adhesion in non-contact dispensing, manufacturers have developed workstations based on many technologies to dispense the droplets – ultrasound, acoustics, piezoelectric, and solenoid.
Liquid handlers with more intuitive software have an important competitive advantage. A great example is the I.DOT system by our customer DISPENDIX. The I.DOT is a non-contact liquid handling automation system and is the first instrument to integrate a built-in drop detection system. The software of the I-DOT was developed in partnership with BioSistemika. The system has become very popular in health and life sciences due to its simplicity and friendly user interface.
Figure 4: DISPENDIX I.DOT (Source: https://dispendix.com)
Every year new products enter the market; therefore, the prices of the systems have dropped. Customers also have more options to choose from and find affordable products for the specific process needed. Competitors are also engaged in developing low-cost liquid-handling robots to gain an advantage in the market.
The adoption of automated liquid handling technologies is anticipated to witness significant growth in the R&D sector, especially in genomic and cancer research. Owing to this increase in the use of automation for drug screening and drug development, pharma and biotech companies are estimated to maintain their lead in the market in the years to come. Demand for automated methods is also anticipated to boost revenue growth in the academic and research institutes segment and Contract Research Organizations (CROs) due to increasing funding and pharmaceutical and biotechnology companies outsourcing them to manage their workflows.
Summary
- Liquid handling systems are the basis of most health and life science laboratories worldwide. Those can be manual, semi-automatic (‘’hybrids’’), or automatic (automated liquid handling (ALH) systems). There are options spanning from small, simple pipettes to full-scale, multifunctional automated workstations.
- Fundamentally, the market is driven by the global expansion of pharmaceutical and biotechnology industries (especially R&D), growth of life science research and favorable funding scenarios in all sectors, and many other reasons. The COVID-19 pandemic additionally boosted the market.
- Pharmaceutical and biotechnology sectors are extensively using liquid handling systems. Especially large- and medium-sized companies are the main driver of the ALH systems market, with increasing investments in R&D to develop novel therapeutics and target drugs.
- Semi-automated liquid handling systems manufacturers enable automation of labs with limited budgets that don’t permit end-to-end automation. Our product PlatR can be a perfect start!
- ALH systems have many benefits – minimizing errors, and variability, improving records and tracking, precision, offering more repeatability, increasing throughput, conserving agents, and reducing hands-on time.
- There are still some challenges of ALH systems – errors can happen, the need for skilled professionals, the high cost of equipment, maintenance, and calibration, and fear that automation might make the day-to-day more challenging.
- Nowadays, ALH systems have improved regarding simplicity with more intuitive software, prices have dropped due to increasing competition, and many novel methods are being introduced.
- There are many opportunities for market players, especially developing more intuitive software to achieve better user experience and faster adoption.
