LinkZill's First Batch of Life Science Product Delivery: Oligo Pools, Microarrays, and Genes

LinkZill has successfully delivered DNA products in three forms based on TFT-DNA synthesis technology

On March 31, 2023, LinkZill's life science business unit was established. Concurrently, the TFT-DNA Synthesizer R&D team was officially founded. On February 26, 2024, the first batch of DNA products based on TFT-DNA synthesis technology was successfully delivered. It took only 11 months from the TFT-DNA synthesizer R&D initiation to the products' commercial delivery. Over the next three weeks, LinkZill intensively completed the delivery of DNA products in three forms, including oligo pools, oligonucleotide microarrays, and DNA fragments (commonly called "genes").

/ Figure: The delivered genes. /

Validation of key product definitions of the TFT-DNA synthesizer with three product forms

TFT chips offer low cost and scalable dimensions (up to approximately 10 square meters). Thus, based on these advantages, TFT-DNA synthesizers can manufacture high-quality DNA with flexible throughput and yield, to accommodate more downstream scenarios including gene assembly, NGS Panel production, high-throughput sequence library screening, single-cell and spatial omics technologies, etc. Compared to the popular piezoelectric inkjet DNA synthesis and CMOS-based electrochemical DNA synthesis technologies, TFT-DNA synthesis technology boosts higher production efficiency and outstanding scalability. In addition to customized DNA products, TFT-DNA also has the potential for batch production of semi-customized and standardized oligo pools and microarray products.

The successful delivery of products by LinkZill has proved the strong association among the TFT-DNA's product definition, technology selection, customers' requirements, and application scenarios.

In many application scenarios, per oligo yield and uniformity of an oligo pool are important technical indicators.In some orders, our customer requested that each oligo in the oligo pool achieve a yield of the picomole scale (100 fmol to 1 pmol), without any post-synthesis amplification or enzymatic digestion process. Therefore, traditional column-based DNA synthesizer produces far more molecules than needed, resulting in significant product waste and higher costs. While existing commercially available high-throughput DNA synthesis technologies cannot achieve the required yield without product amplification. TFT-DNA synthesis technology provides an ideal solution for such demands.

Another way to use TFT-DNA DNA products is to leave DNA molecules on the chip surface as a microarray, to capture and hybridize biomolecules, thereby achieving in situ detection, genotyping, sensing, or other applications. The spot size, density, DNA amount, and signal-sensing methods of the microarray, are also related to different detection sensitivities and ranges.Existing commercialized high-throughput DNA synthesis technologies, such as piezoelectric inkjet, photochemical, and CMOS-based electrochemical routes, are often limited in terms of parameters such as spot density, pitch size, and DNA amount due to the restrictions in the mechanical structure and consumables used in the DNA synthesis solution.

Through LinkZill's in-house TFT patterning, we can produce DNA arrays with varying spot sizes and oligo amounts. On a microarray designed for DNA hybridization, our user can set up detection spots with customized sizes and oligo amounts for the same target, or select different varied ranges for different targets, achieving a balance between the number of targets and a varied detection range using a single detection chip.

Gene assembly requires 15 to 50 oligos as raw materials, with highly uniformed picomole-scale yields (typically 0.2 to 1.0 pmol). These oligos are usually produced using column-based synthesizers, which manufacture at least 1 nanomole product leading to significant waste. The high costs hinder development in areas requiring extensive use of DNA fragments, such as AI-assisted protein design, biomolecular drug discovery, and synthetic biology.

However, most high-throughput DNA synthesizers can only produce oligos at the scale of 0.1 femtomoles, far from meeting the gene assembly requirement. To perform gene assembly, such technical routes always need two rounds of amplification, error correction, and restriction enzyme digestion, making the experimental process more cumbersome. The unevenness of the oligos is also exponentially amplified, resulting in a low success rate, a higher error rate introduced by spot crosstalk and amplification, and a much higher validation cost during gene assembly. Therefore, few high-throughput DNA synthesis technologies can produce oligo pools capable of gene assembly. Even if some technical route is feasible, the production cost, labor cost, delivery cycle, and sequence compatibility are not superior to the column-based method.

Delivery genes with a high success rate, lower cost, and faster cycle, without oligo pool amplification, is one of the "killer applications" targeted by TFT-DNA synthesis technology. We have successfully assembled and validated genes using amplification-free oligo pools and pools with one-round amplification, whose lengths range from 1.0 to 1.5 kb.

Based on dynamic programming algorithms, LinkZill has developed gene sequence and oligo pool design pipelines to accommodate over twenty gene assembly protocols, greatly improving the success rate of gene assembly using TFT-DNA synthesis products. It is expected that on 4K and 65K throughput TFT-DNA chips, LinkZill will reduce the cost of gene assembly to around 0.03 to 0.07 RMB/bp, which includes reagent, consumables, and sequencing. This brought about a fundamental supply chain revolution for large-scale gene synthesis applications, such as AI-assisted protein design, antibody screening and nucleic acid drug screening, synthetic biology, etc.

Booming R&D progress of TFT-DNA synthesis equipment and chips

In device R&D, LinkZill has developed eight Alpha-testing TFT-DNA synthesizers belonging to five generations in just eight months. Inter-device and inter-batch variances have been well controlled, marking the perfect conclusion of the Alpha testing phase.

We are also about to start the development of Beta testers. In the near term, Beta testers will cover two major models: a benchtop R&D device, and a multi-channel industrial device. In the future, we will also initiate the technical verification of a large-dimensional model for mass production. By 2024Q2, we expect to complete the shipment of several TFT-DNA synthesizers, TFT-DNA chips, and proprietary reagents, and commence Beta testing in end-customer labs.

/ Figure: LinkZill's Benchtop TFT-DNA Synthesizer. /

In addition to completing the verification and product delivery of TFT-DNA chips with throughputs varied from 64 to 4K, we have also completed the design of dozens of different versions of chips, covering 65K, 131K, and 262K throughputs, whose manufacture and testing which will be completed in Q2 to Q3 of 2024.

More life science tools and standardized services are coming soon, stay tuned

To continuously iterate the TFT-DNA synthesizer and its supporting tools, and verify the application value of TFT technology in various R&D, testing, and production scenarios, we will also launch standardized commercial services later this year, including oligo pools, oligonucleotide microarrays, gene library design and construction, etc.

Please pay attention to our WeChat public account and website to get our latest progress in real-time.We warmly welcome everyone to become an angel user of the TFT technology in life sciences, join us in linking zillions of technologies, and lead the next transformation.