In a groundbreaking study published in Advanced Science, our customers at Paris-PSL Research University have unveiled a transformative approach to synthetic biology that leverages advanced automation technologies (Fig. 1).
Exponential DNA amplification techniques are crucial for ultrasensitive molecular diagnostics due to their wide dynamic range, but they require real-time monitoring for accurate quantification. On the other hand, linear amplification methods, while less sensitive, enable quantitative measurements from a single end-point readout, making them ideal for low-cost, point-of-care, or large-scale testing. Combining the high sensitivity of exponential amplification with the simplicity of end-point detection could overcome a major design challenge, paving the way for a new generation of scalable quantitative bioassays. In this context, a novel hybrid nucleic acid-based circuit design is presented, capable of computing a logarithmic function to achieve a broad dynamic range with just a single end-point measurement.
The CELIA (Coupling Exponential Amplification reaction to LInear Amplification) system utilizes a flexible biochemical circuit architecture that couples a customizable linear amplification stage—potentially incorporating an inverter function—with an exponential module in a single-pot format. When applied to microRNA detection, CELIA achieves a femtomolar limit of detection and a dynamic range spanning six orders of magnitude. This isothermal method eliminates the need for thermocyclers without sacrificing sensitivity, making it suitable for various diagnostic applications and providing a streamlined, cost-effective, and high-throughput solution for quantitative nucleic acid analysis.
At the heart of this innovation is DISPENDIX's I.DOT, a non-contact liquid handling robot that is redefining how scientists approach high-throughput applications like DNA assembly.
Figure 1. "Coupling Exponential to Linear Amplification for Endpoint Quantitative Analysis" research paper published in Advanced Science.
Synthetic biology has long held the promise of engineering biological systems for various applications, from developing new pharmaceuticals to creating sustainable biofuels. However, one of the primary challenges in this field has been the complexity and labor-intensive nature of DNA assembly and manipulation. Traditionally, these processes have required significant manual input, resulting in time-consuming and error-prone workflows. Researchers are constantly seeking ways to streamline these steps, and this is where DISPENDIX's I.DOT technology enters the scene.
Pairs of concentrations for let-7a and miR-203a were randomly chosen in the logarithmic range between 10⁻¹⁴ and 10⁻¹² M. Sample preparation was carried out using the I.DOT Non-Contact Dispenser, an automated liquid handling robot, in a 384-well plate (Bio-Rad), guided by a custom-made script.
The I.DOT Non-Contact Dispenser has emerged as a game-changer in the field of synthetic biology, enabling researchers to achieve unprecedented levels of precision and efficiency in liquid handling. The study highlights how the I.DOT was employed for the rapid and accurate dispensing of reagents in the process of high-throughput DNA assembly.
By leveraging the I.DOT’s capability to dispense ultra-low volumes of liquids (down to nanoliters) with high accuracy, the researchers were able to automate DNA assembly processes, drastically reducing the amount of time required for setup and execution. The non-contact nature of the I.DOT’s dispensing technology also minimizes the risk of cross-contamination, a critical consideration in synthetic biology experiments where purity and precision are paramount.
Speed and Efficiency: With its high-speed dispensing capabilities, the I.DOT significantly reduces the time required for setting up experiments. This is particularly beneficial in high-throughput scenarios where hundreds or even thousands of samples need to be processed quickly.
Accuracy and Precision: The non-contact dispensing technology ensures that even the smallest volumes are delivered accurately. This level of precision is crucial when working with expensive or rare reagents, allowing for cost-effective and efficient experimental designs.
Scalability: The I.DOT is highly versatile and can easily scale to accommodate different experimental setups. Whether it's small-scale pilot studies or large-scale projects, the I.DOT can handle the varying demands of different research phases.
Reduced Risk of Contamination: The I.DOT’s non-contact liquid handling mechanism helps maintain a sterile environment, reducing the chances of contamination and ensuring the integrity of the experimental results.
The integration of the I.DOT in synthetic biology workflows represents a significant leap forward in the automation of biological research. By automating and optimizing liquid handling tasks, researchers can focus more on analysis and discovery rather than being bogged down by repetitive manual processes. This technological advancement opens the door to new possibilities in synthetic biology, including more complex and high-throughput experiments that were previously too challenging or costly to perform.
The use of the I.DOT in this recent study highlights the transformative potential of automated liquid handling technology in synthetic biology. For researchers looking to push the boundaries of synthetic biology, the I.DOT represents not just a tool, but a gateway to new scientific frontiers.
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Wang, L., Perez, K. J., Villari, J., Gao, Y., Varady, E., & Mutlu, H. (2024). Photochemical programming of responsive materials via light‐induced crosslinking and trans‐esterification. Advanced Science, 2309386. https://doi.org/10.1002/advs.202309386