What is automation in high-throughput science?
Author: Tori Reynolds
Learning Objectives
- Describe high-throughput automation
- List the pros and cons of automation in comparison to manual labor
- Evaluate the significance of automation in science
Graphical Abstract
Legend. Automation in high-throughput science is the use of machines to perform laboratory tasks with very little manual labor.1 Benefits of automation compared to manual labor in high-throughput science include increased efficiency, increased speed, better reproducibility, decreased error rates.1-8 A comparison can be made between automatic and manual pipetting in which manual pipetting is slow and error-prone while automatic pipetting is quick and efficient. The image in the top left corner is a visual representation of the benefits of automation. The image in the bottom right corner displays automatic pipetting into a microplate. (Images are reused from Shutterstock for educational purposes only). Image created with Canva Pro.
Summary
Introduction
Automation is the process of using machines, such as liquid handlers, to perform aspects of experiments, such as pipetting and imaging. It is an integral part of high-throughput discovery as it vastly improves efficiency and speed of laboratory tasks that are usually performed manually.1 Automation is commonly included in protocols for high-throughput screening, but is becoming increasingly important for other applications.1
Automating protocols allows for better reproducibility, increased speed, increased accuracy, and fewer staff members.2,3 However, errors are still possible in an automated experiment because a human has to calibrate the machines.2 Manual lab work is time-consuming and has a higher risk of human error.2,3 Automation and high-throughput science are associated with high start-up costs as the equipment and machines are very expensive, but there is a quick return on investment due to the increased productivity and decreased staff members needed in the laboratory.1
Applications
Automation has a vast array of applications and more applications are being consistently developed as high-throughput science expands. The importance of automation is the ability to increase throughput and decrease error rates. Current applications for automation include cancer research, whole blood and DNA processing, plant phenotyping, molecular breedings of plants, colony and cell counting, drug discovery, pharmaceutical development, and more.2-8
Cancer research has been greatly impacted by the implementation of automated protocols, especially studies on cancer stem-like cells.4 A tumor sphere assay chip has been developed that allows for around 10,000 cells to be tracked in order for a representative sample to be taken.4 The tracking and analysis of stem-like cells allows for a correlation to be drawn between cell size, cellular heterogeneity, and cancer development.4 The sphere assay chip and automatic imaging is useful for measuring and identifying cancer stem-like cells in order to gain a better understanding of these cells.4
Whole blood and DNA processing to create DNA databases has historically been very tedious and time-consuming, but with recent developments in high-throughput automation much of the steps associated with these processes can now be automated.3 The Total Laboratory Automation system developed by Xiao is capable of performing sample barcoding and scanning, DNA extraction, PCR setup, heat sealable filming, centrifugation, PCR amplification, capillary electrophoresis, and analysis automatically.3 The ability to perform all of these tasks automatically allows for less error, fewer staff, and less cross-contamination due to the closed design.3 This system allows for a greater number of samples compared to manual labor to be fully set up and analyzed to construct large DNA databases.3
Plant phenotyping is important for plant biologists to understand how the genome and the environment result in the traits that can be seen in the plant.5 Automation can be applied to this science through the use of machines that automatically grow, observe, image, and analyze a large number of plant samples.5 The large-scale analysis made possible by automation makes it possible to monitor changes of the plant samples over time.5 Another application of automation in plant science is the ability to perform better, faster molecular plant breedings.6 These plant breedings in corn allow for certain growth promotion genes to be selected for.6
Cell and colony counting is slow and is not feasible for high-throughput science, which is one way in which automation can be applied to improve experiments.2 Automating cell and colony counts is made possible by a machine taking digital images of wells.2 The images are then analyzed by the machine.2 Automated counts can provide information about microbial and toxin content, as well as gene functionality.2 A benefit of using automation for cell and colony counting is that these counts are more accurate and are reproducible.2
Zebrafish embryos have been used in drug discovery for in vivo screenings to test compounds in an intact organism with a natural physiological environment as opposed to in vitro conditions that are artificial.7 A machine monitors embryos, delivers compounds of interest to the embryos, incubates, images, and analyzes fluorescence to determine the effect of the compound on the organism.7 Chinese Hamster Ovary (CHO) cells are commonly used in pharmaceutical studies to aid in development and monitor the effects of the pharmaceutical on a mammalian cell model.8 With automation, five times more CHO cell clones can be screened in the same amount of time with less staff.8 Drug discovery and pharmaceutical development are two of the most common applications of automated high-throughput science.7,8
Conclusion
Automation is very useful and has a lot of practical applications throughout high-throughput science.1-8 The implementation of automated protocols allows for increased efficiency and reproducibility of experiments.1-8 Many manual laboratory practices, such as pipetting and cell counting, are impractical for use with high-throughput science and are associated with a higher error rate due to human mistakes.2-8 Therefore, the use of automation has become an important aspect of advancing high-throughput studies.1-8
References
1) Glökler, J., Schütze, T., & Konthur, Z. (2010). Automation in the High-throughput Selection of Random Combinatorial Libraries—Different Approaches for Select Applications. Molecules, 15(4), 2478-2490. doi:10.3390/molecules15042478
2) Choudhry, P. (2016). High-Throughput Method for Automated Colony and Cell Counting by Digital Image Analysis Based on Edge Detection. Plos One, 11(2). doi:10.1371/journal.pone.0148469
3) Xiao, L. (2019). Designing and implementing a large-scale high-throughput Total Laboratory Automation (TLA) system for DNA database construction. Forensic Science International, 302, 109859. doi:10.1016/j.forsciint.2019.06.017
4) Cheng, Y., Chen, Y., Brien, R., & Yoon, E. (2016). Scaling and automation of a high-throughput single-cell-derived tumor sphere assay chip. Lab on a Chip, 16(19), 3708-3717. doi:10.1039/c6lc00778c
5) Lee, U., Chang, S., Putra, G. A., Kim, H., & Kim, D. H. (2018). An automated, high-throughput plant phenotyping system using machine learning-based plant segmentation and image analysis. Plos One, 13(4). doi:10.1371/journal.pone.0196615
6) Wang, H., Liu, J., Xu, X., Huang, Q., Chen, S., Yang, P., . . . Song, Y. (2016). Fully-Automated High-Throughput NMR System for Screening of Haploid Kernels of Maize (Corn) by Measurement of Oil Content. Plos One, 11(7). doi:10.1371/journal.pone.0159444
7) Letamendia, A., Quevedo, C., Ibarbia, I., Virto, J. M., Holgado, O., Diez, M., . . . Callol-Massot, C. (2012). Development and Validation of an Automated High-Throughput System for Zebrafish In Vivo Screenings. PLoS ONE, 7(5). doi:10.1371/journal.pone.0036690
8) Wang, B., Albanetti, T., Miro‐Quesada, G., Flack, L., Li, L., Klover, J., . . . Hawley‐Nelson, P. (2018). High‐throughput screening of antibody‐expressing CHO clones using an automated shaken deep‐well system. Biotechnology Progress, 34(6), 1460-1471. doi:10.1002/btpr.2721
Audio Recordings
Introduction (2:17 min)
Applications (4:59 min)
Conclusion (1:01 min)
Questions
- What is high-throughput automation? High-throughput automation is the use of machines to perform laboratory tasks in order to increase throughput.
- What are the benefits of using automated science? Automated protocols allow for higher reproducibility, increased speed, increased accuracy, and decreased error.
- Compare and contrast automated, machine pipetting and manual, human pipetting. Machine pipetting is fast, accurate, and efficient. The machines are very expensive to purchase and still have a risk for human error because humans are required to program the machines. Human pipetting has an increased risk of error, is time-consuming, and is labor-intensive. The equipment needed for human pipetting is inexpensive, however labor is expensive.