Synthetic Biology

The Role of Automated Liquid Handling in Gene Synthesis

Discover how automated liquid handling enhances gene synthesis, offering speed, accuracy, cost savings, and high throughput.

Gene synthesis is a fundamental component of synthetic biology applications1. It involves the generation of a pre-designed genetic sequence and impacts many fields, including biomedical research and agriculture (Fig. 1)2. Gene synthesis offers researchers many advantages over conventional techniques. With gene synthesis, sequences are fully customizable and can include complex regions such as long repetitive sequences and those with high GC content. Traditional cloning techniques take far longer, are less reliable, and generate unwanted mutations. This means that gene synthesis offers researchers significant advantages and helps to speed up research projects.

The combination of gene synthesis and automated liquid handling offers significant power to researchers. These technologies perfectly complement each other by facilitating faster research projects, minimizing the chance of error, and enhancing research confidence. The I.DOT Liquid Handler is an ideal automated tool for gene synthesis workflows that provides researchers with accuracy and fast turnaround times. In this blog, we will discuss how automated liquid handling can streamline gene synthesis and how these technologies synergize to advance research.

Figure 1. Gene synthesis technologies have revolutionized several fields by providing fully customizable sequences with less error than conventional methods. (Source)

Automated Liquid Handling in Action

Automation3 improves several aspects of gene synthesis procedures, including reagent dispensing, solution mixing, and sample preparation (Fig. 2).

Reagent Dispensing

Accurate reagent dispensing is essential for experiment success in gene synthesis workflows. Enzymes and nucleotides must be added at precise concentrations to achieve consistent results. Accurately dispensing tiny volumes offers the advantage of scaling down experiments for resource maximization. However, managing these low volumes is incredibly difficult using manual methods. Automated liquid handling machines like the I.DOT Liquid Handler allow for accurate non-contact dispensing of volumes as low as 10 nL, ensuring consistency within and across experimental runs. Furthermore, rapid and precise reagent dispensing facilitates high-throughput workflows that generate vast amounts of reliable data and help researchers reach their goals faster.

Learn more about the I.DOT Non-Contact Dispenser

Solution Mixing

Managing and effectively mixing multiple complex ingredients poses a significant challenge for gene synthesis workflows. Errors come with a high cost in terms of resources and time. Automated liquid handling ensures solution homogeneity, which helps establish experiment consistency. Efficiency in reagent management and mixing ensures that reagents are stored at suboptimal conditions for shorter periods and are less prone to degradation. Furthermore, automation allows researchers to control the mixing protocol, which helps reduce reagent damage due to excessive heat or vortexing.

Sample Preparation

Automation significantly speeds up sample preparation, comprised of many steps that usually require manual input. These include purification, quantification, and quality control. Automated liquid handling allows these processes to be performed as an integrated workflow within gene synthesis experiments and means that many samples can be processed simultaneously. This facilitates high-throughput sample processing while freeing up researcher time for planning experiments and analyzing data.

Figure 2. Manual pipetting is time-consuming and inherently error-prone, and it lacks the scalability and resource efficiency of automated workflows.

Benefits of Automation

Automation provides numerous benefits for researchers performing gene synthesis workflows (Fig. 3). These include:


Manually pipetting gene synthesis workflows is incredibly time-consuming, especially with large numbers of samples. Automated workflows can be programmed for long experiments that run overnight without researcher input. Ultimately, these factors significantly increase laboratories' research output. 


Automated liquid handling reduces human error by eliminating the need for manual pipetting. It also allows researchers to control environmental parameters that match vendor instructions, improving accuracy. Furthermore, automated workflows are entirely programmable, so researchers can run the same program for gene synthesis across different runs to ensure inter-run accuracy and reproducibility. Built-in quality checks also prevent the dispensing of incorrect volumes, which can negatively impact the end product of gene synthesis experiments.

Cost Reduction

Automation facilitates cost reduction of gene synthesis in several ways. Firstly, automated liquid handling, which uses microfluidic capabilities4, allows researchers to scale down their workflow and generate more results while using fewer expensive reagents like polymerase enzymes. Furthermore, by removing the possibility of human error, automation means that researchers rarely need to repeat gene synthesis experiments due to improper dispensing or not following procedures correctly. By freeing up time, automation allows researchers to allocate work hours to other aspects of their research, allowing for more efficient use of human resources.

High-throughput Capabilities

Automation facilitates high-throughput sample processing5, allowing researchers to streamline their gene synthesis workflows and speed up their research goals. This is particularly useful in the generation of large libraries of genetic sequences. Importantly, faster research output does not come at the expense of quality with automated liquid handling capabilities.


DISPENDIX I.DOT Liquid Handler

Figure 3. The I.DOT Liquid Handler gives researchers the power of automation with a user-friendly interface.


Integrating automated liquid handling in gene synthesis workflows offers transformative advantages, including increased speed and accuracy, cost reduction, and high-throughput capabilities. Technologies like the I.DOT Non-Contact Dispenser can streamline complex processes such as reagent dispensing, solution mixing, and sample preparation. This synergy between gene synthesis and automation not only accelerates scientific discoveries but also enhances the overall quality and reproducibility of research outcomes, driving advancements in synthetic biology and beyond. Future advancements in this area will focus on optimizing the synthesis of megabase lengths of DNA6 and implementing gene synthesis for personalized medicine7.

Ready to unlock the power of automation in your gene synthesis workflow?

The I.DOT Liquid Handler offers unmatched precision and ease of use, making it the perfect tool for researchers of all experience levels. With its non-contact dispensing as low as 4 nL and integrated droplet detection, the I.DOT ensures accuracy and eliminates waste, saving you time and precious resources.

Book a demo today to learn more about the I.DOT Liquid Handler and how it can revolutionize your gene synthesis research!


  1. Meng F, Ellis T. The second decade of synthetic biology: 2010–2020. Nat Commun. 2020;11(1):5174. doi:10.1038/s41467-020-19092-2
  2. Hughes RA, Ellington AD. Synthetic DNA Synthesis and Assembly: Putting the Synthetic in Synthetic Biology. Cold Spring Harb Perspect Biol. 2017;9(1):a023812. doi:10.1101/cshperspect.a023812
  3. Holland I, Davies JA. Automation in the Life Science Research Laboratory. Front Bioeng Biotechnol. 2020;8(571777). doi:10.3389/fbioe.2020.571777
  4. Duncombe TA, Tentori AM, Herr AE. Microfluidics: reframing biological enquiry. Nat Rev Mol Cell Biol. 2015;16(9):554-567. doi:10.1038/nrm4041
  5. Blay V, Tolani B, Ho SP, Arkin MR. High-Throughput Screening: today’s biochemical and cell-based approaches. Drug Discovery Today. 2020;25(10):1807-1821. doi:10.1016/j.drudis.2020.07.024
  6. Ma Y, Zhang Z, Jia B, Yuan Y. Automated high-throughput DNA synthesis and assembly. Heliyon. 2024;10(6):e26967. doi:10.1016/j.heliyon.2024.e26967
  7. Allen S, Garrett A, Muffley L, et al. Workshop report: the clinical application of data from multiplex assays of variant effect (MAVEs), 12 July 2023. Eur J Hum Genet. 2024;32(5):593-600. doi:10.1038/s41431-024-01566-2

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