Robotic PCR Achieves High-Fidelity DNA Amplification for Data Storage Applications

Polymerase chain reaction, a cornerstone of modern biology, currently relies on equipment that presents hurdles for emerging fields like DNA data storage, which demands complete automation and affordability. Vincent Beguin, Jean Grétillat, and Kornelija Kaminskaitė, alongside their colleagues at various institutions, now present a radically simplified approach to PCR amplification. Their team reimagines the original water bath method, integrating it with precise robotic liquid handling to perform the entire process within sealed pipette tips, immersed and withdrawn from a single, temperature-controlled oil bath. The results demonstrate amplification efficiency and sequencing accuracy matching conventional, high-performance thermocyclers, while simultaneously minimising waste, reducing contamination and offering a scalable, cost-effective solution for applications ranging from data storage to diagnostics.

DNA Encoding With Galois Field Codons

This research details a system for storing digital data within DNA sequences, utilizing a unique encoding scheme. Data is divided into 2-byte chunks and converted into 9-nucleotide symbols using a Galois Field (GF(41)) codon wheel, ensuring sequence diversity and minimizing repetition. Each DNA strand, or oligonucleotide, incorporates forward and reverse primers for amplification, 207 nucleotides for data, error correction codes, and an index for file identification. This system can handle large files, up to 146 GB, by dividing them into manageable blocks and packaging the encoded data into an OLOS format for organization and retrieval.

The team successfully encoded a DNAMIC logo as a test, demonstrating the system’s functionality. Error correction is achieved using Reed-Solomon codes, which account for errors introduced during DNA synthesis, preservation, PCR, and sequencing, with adjustable redundancy levels based on observed error rates. Primers are carefully designed using a hash function to maximize PCR efficiency and minimize unintended interactions, while the use of GF(41) is fundamental to the binary-to-DNA conversion process. Detailed analysis of thermal effects on the system’s components confirms the importance of precise temperature control during amplification.

PCRobot, Sealed Pipette Tip Amplification System

Scientists have pioneered a new approach to polymerase chain reaction (PCR) by integrating robotic liquid handling with a simplified thermal cycling method, revisiting the original water bath technique. This innovation addresses limitations in automation, contamination control, and cost-effectiveness, particularly for applications like DNA data storage. The system, named PCRobot, performs complete amplification within sealed pipette tips, eliminating the need for complex thermal management systems found in conventional thermocyclers. PCRobot utilizes a robotic unit to precisely immerse and withdraw pipette tips into a single, temperature-controlled oil bath, facilitating the denaturation, annealing, and extension steps of PCR. Experiments demonstrate that this technique achieves amplification efficiency and sequencing fidelity comparable to high-performance thermocyclers when applied to DNA-encoded datasets. The system minimizes reagent waste and contamination risks through complete tip isolation, offering full sample recovery and a modular, automation-ready platform for end-to-end DNA data storage workflows.

PCRobot Achieves Automated, Efficient DNA Amplification

Researchers have developed PCRobot, a novel PCR platform integrating robotic liquid handling with a simplified thermal cycling approach. This system revisits early PCR methods employing water baths, combining them with automated systems to achieve full automation and minimize contamination. PCRobot performs amplification entirely within sealed pipette tips, immersing and withdrawing them from a single, temperature-controlled oil bath, eliminating the need for complex thermal management systems. Experiments reveal that PCRobot achieves amplification efficiency comparable to high-performance thermocyclers when used with DNA-encoded datasets.

Measurements demonstrate an amplification efficiency of 0.686, a statistically significant improvement compared to a conventional thermocycler. Post-purification DNA concentrations were also higher with PCRobot, confirmed by statistical analysis. Temperature monitoring shows that PCRobot maintains precise temperature plateaus, and while cooling rates are slower, the system completes 25 cycles in approximately 60 minutes, consuming only slightly more energy than a conventional thermocycler. This modular design offers a scalable and cost-effective solution for applications including DNA data storage and diagnostics.

PCR Automation via Robotic Liquid Handling

This research presents a novel approach to PCR, integrating amplification directly into a robotic liquid-handling system and moving away from traditional thermocyclers. The team successfully demonstrated that this new platform, termed PCRobot, achieves comparable amplification efficiency and sequencing fidelity to established methods when used with DNA-encoded datasets. By performing thermal cycling within sealed pipette tips immersed in a single temperature-controlled oil bath, the system simplifies thermal management and enables full automation, addressing key challenges for DNA data storage and high-throughput diagnostics. The design minimizes contamination risks through complete tip isolation and enhances automation compatibility by embedding thermal cycling within existing robotic infrastructure. Statistical analysis revealed no significant difference in decoding performance or sequencing reads compared to conventional thermocyclers, highlighting the potential of redesigning molecular biology protocols for integration into automated systems, paving the way for more robust, sustainable, and scalable technologies in life sciences.