It is a well-known fact that innovation in the life science industry is primarily driven by advanced technologies that possess the tendency to maximize assay throughput and frequency. There are several environmental factors and process variables that may influence or obstruct appropriate liquid handling, which further compromises the integrity of the solution under process. Therefore, it becomes important to preserve asepsis throughout the liquid handling procedure and ensure that the integrity of the solution is not compromised. Since long, liquid handling has been a manual process, which has several disadvantages and limitations, including risk of human error, exposure to radioactive materials / harmful chemicals, and lower ergonomic safety. Over time, with growing demand for liquid handling systems and stringent regulatory guidelines, the biopharmaceutical industry has shifted to using automated liquid handling systems, which offer a reliable method for dispensing and aspirating the solution directly from the pipette to the tube or well. Further, automated liquid handling systems have the capability to dispense liquid volumes (up to nanoliters) with great precision and accuracy. Owing to these advantages, there has been an increased demand for such systems in research laboratories, universities and the clinical research industry. The global automated liquid handling systems market is anticipated to grow at a CAGR of 7.4%, till 2035, according to Roots Analysis. Driven by the rising interest of stakeholders in technological advancements and adoption of automated liquid handling systems, the overall automated liquid handling market is likely to witness significant growth during the forecast period.
INTRODUCTION TO AUTOMATED LIQUID HANDLING SYSTEMS
Automated or robotic liquid handling systems are devices used for dispensing and sampling liquids in tubes or wells. Owing to the greater precision and reproducibility offered by automated liquid handling systems as compared to manual systems, several laboratories have shifted towards automating different steps involved in liquid handling. Primarily, there are two types of automated liquid handling systems, including automated pipetting systems and automated microplate washers. These systems offer accurate sample preparation for various bioassays, high-throughput screening / sequencing (HTC), next-generation sequencing, liquid or powder weighing, and maintenance or storage of large samples.
AUTOMATED PIPETTING SYSTEMS
Automated pipetting systems are liquid handling instruments that are frequently used for copying, pooling, mixing and performing serial dilution of liquids. An automated pipetting system speeds up the pipetting / dispensing of liquid as compared to the manual pipetting method. Moreover, the automated pipetting systems have resulted in enhanced workflow accuracy for various types of liquid and volume ranges.
TYPE OF AUTOMATED PIPETTING SYSTEMS
Tip-based Pipetting: It involves three different mechanisms, namely contact pipetting, air displacement and piston displacement. Contact pipetting involves the touch-off of the dispensing tip in order to release the liquid. Whereas in air displacement pipetting, samples are separated from mechanical parts through an air cushion and other alternatives, such as filter tips to minimize the risk of cross-contamination. It allows sample transfer as well as mixing. The piston / positive displacement method works well for all types of samples, allowing sample transfer and mixing by using disposable tips that minimize cross-contamination risks and enables accurate and repeatable pipetting.
Non-tip-based Pipetting: The non-tip-based pipetting technology involves acoustic droplet ejection and digital ink-jet dispensing mechanisms. Acoustic droplet ejection method only allows sample transfer and enables non-contact sample transfer (up to microliters and nanoliters) of all types of liquids using the sound energy. It results in more accurate and precise biological activity in pharmacological studies when compared to tip-based dispensing. Whereas digital ink-jet dispensing method enables the distribution of independently dosed droplets into individual wells, without the need for serial dilution. It provides flexibility and accuracy in dispensing very low sample volumes.
ADVANTAGES OF AUTOMATED PIPETTING SYSTEMS
Key advantages of automated pipetting systems include:
- Time Saving: Automated pipetting systems enable high throughput and are ready to use in labs in less amount of time.
- Cost Savings: Automated pipetting systems with interchangeable pipette heads offer a practical solution to reduce labor related cost.
- Improved Lab Safety: They minimize the user involvement thereby reducing exposure and cross contamination.
- Improved Accuracy: They reduce the test variability between multiple operators, thereby enhancing assay reproducibility and accuracy results.
AUTOMATED MICROPLATE WASHERS
Automated microplate washers are designed to profile microplates automatically, which results in the elimination of human error from the process. This enables accurate microplate positioning and offers high-quality performance during wash cycles. Further, since the microplates are available in a variety of sizes (96, 384, and 1,536 well plates), automated microplate washers can read, interpret the size of the microplate and proceed with the appropriate cleaning method. On the other hand, some designs of automated microplate washers may require additional hardware components in order to process different microplate styles.
FEATURES OF AN IDEAL AUTOMATED MICROPLATE WASHER
The features of an ideal automated microplate washer include:
- Ability for Performing Multiple Custom Dispensing: Multiple custom dispensing minimizes the residual volume which may result in high background signals during an assay.
- Touchscreen User Interface: The presence of a touchscreen user interface in an automated microplate washer enables easy programming of the wash procedure.
- In-built Sensors: The sensors for liquid level detection can prevent the fluid from overflowing and reduce the risk of instrument the malfunction
- Software Integration: The software monitors different stages of the workflow, records the data to a common database and supports integration with other instruments.
- Bead-based Assays: Automated microplate washers can aspirate the liquid in wells when using bead-based assays in the laboratory without the chances of losing the beads.
APPLICATIONS OF AUTOMATED LIQUID HANDLING SYSTEMS
Automated liquid handling systems are frequently used for protocols, such as RNA / DNA purification, ELISA, cell culture, PCR / automated detection assays and protein purification. Given their diverse applications across biological research, pharmaceutical industry, and genomics, automated liquid handling systems have been recognized as one of the most effective liquid handling systems.
The automated liquid handling systems have applications in various industrial segments; these include:
- Biological Research: Automated liquid handling systems help to reduce contamination risks and allow efficient completion of mixing and pipetting steps.
- Molecular Biology Assays: The amplification discrepancies in manual pipetting often impact PCR results. Such cases can be avoided by employing automated liquid handling systems as they provide accurate results.
- Epigenetics and Genetics: Several automated liquid handling devices and second-generation sequencing technologies have been developed for epigenetic-based treatment of diseases.
- Pharmaceutical Industry: The liquid handling robots accurately control the volume of dispensed liquid and result in a significant reduction in material-related costs in the drug development process.
CHALLENGES IN ADOPTION OF AUTOMATED LIQUID HANDLING SYSTEMS
Over the past century, the structure of the pipette has witnessed significant developments, ranging from Pasteur to air displacement and multichannel; with the latest development being an automated liquid handling robot. Although automated pipetting systems / liquid handling systems have recently gained popularity as they provide increased throughput and reproducibility, these systems have certain limitations that have hindered their adoption across various scientific laboratories. Furthermore, due to the complexity associated with automated liquid handling systems, many end-users are discouraged from adopting these systems. The adoption of such systems requires extensive programming knowledge and follow rigid automation protocols. The challenging process of developing such systems often stems from the user interface of the supporting software. Moreover, the programming languages provided by manufacturers may not be user-friendly for biologists, limiting the use of these devices to automation engineers. Consequently, the utilization of automated liquid handling systems becomes more difficult, leading to increased operator costs. As automated liquid handling systems are expected to cater to specialized needs in the pharmaceutical industry in the coming years, the primary obstacle lies in developing standardized and user-friendly solutions.
FUTURE PERSPECTIVES
The automated pipetting systems and automated microplate washers are paving the way for technologically advanced pharmaceutical laboratories. Since the guidelines for pharmaceutical liquid handling are constantly evolving, particularly in the areas of digitalization, automation, and process transparency, the need for automated liquid handling systems is growing. In addition, the capability of automated liquid handling systems to access all relevant process data in real time is anticipated to revolutionize this industry. Further, the ability to handle small amounts of liquid more efficiently and the growing demand for miniaturization are likely to be the key growth drivers in the automated liquid handling domain.
The upcoming innovations in automated liquid handling require the implementation of artificial intelligence to manage various stages of the procedure and to fully utilize internet connectivity to communicate with users remotely. Since its introduction as a method to control the flow of a liquid through filter paper, automated liquid handling has addressed the fundamental need of increasing experimental productivity by processing large numbers of samples quickly and accurately. The latest instruments are anticipated to respond to sudden changes in procedures in a manner similar to human beings, paving the way for laboratories containing fully automated liquid handling systems, along with robotized modules that can handle majority of the practical tasks.
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