What’s the madness behind growing DNA on "cell phone screens" ?

Originally published by 36kr

Edited and translated by LinkZill

Transboundary innovation is becoming an important strategic initiative for global industrial upgrading, and has also become the layout direction of many current innovative enterprises. How to make the technology and talents in different fields realize truly effective cross-fertilization and stimulate the potential of innovation is a difficult problem and an opportunity in front of every entrant.

The development trend of the global semiconductor industry predetermines that TFT semiconductors (Thin-Film Transistor, widely used in the control of LCD screens) will definitely be applied to life sciences on a large scale at some stage.LinkZill has gathered a group of innovators with interdisciplinary backgrounds and appeared at a very good point in time and industrial chain position.

Navigating the 'No Man's Land': A Group of 'Mavericks' in Cross-Border Endeavors

"In terms of technology selection, TFT semiconductor demonstrates unique advantages when applied in the field of life sciences. We hope to use semiconductors to open up the bottleneck in the integration of life science tools in the build and test process."

On the morning of November 28th, at the WISE 2023 Business Conference, Dr. Linrun Feng, Founder and Co-CEO of LinkZill, shared his thoughts and practical experience on transboundary innovation around the theme of "Bidirectional Journey of Semiconductors and Life Sciences".

Why choose to cross over from semiconductors to life sciences?

Looking back at the recent developments in the field of life sciences, we can observe a gradual semiconductorization of many tools. Silicon-based semiconductors are a well-known technology selection. They possess characteristics such as high precision, high throughput, and a small footprint. This technology can significantly reduce reagent consumption, facilitate high-throughput parallel reactions, and acquire precise photonic signals.

However, the greater amount of work in this field, which is not aimed at acquiring signals but rather molecules and cells, requires larger reaction loads. For example, to construct reaction systems, small area chips are difficult for such work, and as a disposable consumable, the market space will be limited if silicon-based chips cannot solve the problem of high cost.

In this scenario, the industry urgently needs to find solutions that combine high throughput, large area, and low cost, apart from silicon-based semiconductors. TFT semiconductor inherently possess these advantages, making it the best choice for applications requiring a "throughput and yield balance" and "full-process integrated tools."

But from semiconductor cross-border to the field of life sciences is not easy, TFT semiconductor applications in the field of life sciences before is rare, the lack of mature experience, coupled with interdisciplinary cross-fertilization, this is undoubtedly a "no man's land" of the long journey.

As a pioneer in the field of semiconductors, LinkZill has decided to enter the field. As the first link in the build-test integrated toolchain, "DNA synthesis" is the first step in this long journey, and also the first application scenario to realize "flux-load balance" verification.

Focusing on this direction, LinkZill successfully launched the first TFT-DNA desktop synthesizer in mid-September this year, and completed the development of four electrically-controlled TFT-DNA synthesizer Alpha testers, which successfully realized 200nt high-quality DNA synthesis, with a coupling efficiency of 98.5% and a single-pixel-point yield at the pmol level, and, through the physical partitioning of the chip, the first realization of The parallel gene splicing without amplification of oligonucleotide libraries has been realized for the first time by physical partitioning of the chip.

Under these technical specifications, LinkZill is poised to deliver oligonucleotide libraries with advanced technical metrics, such as achieving a single-pixel yield at the picomole scale and achieving oligo pools with lengths over 300 nt. This capability has the potential to unlock the application scenarios of this technology in synthetic biology, AI-assisted protein design, cell and gene therapies, nucleic acid and polypeptide drug discovery, spatial genomics and other fields.

"The journey is indeed challenging. So, when choosing this untrodden path, outsiders might think I'm 'crazy,' but behind all my 'madness,' there is robust logic to support it," said Dr. Linrun Feng in an interview with 36Kr. Leveraging China's significant capacity and cost advantages in the TFT semiconductor manufacturing industry, with over 70% of global capacity based on the Chinese mainland, and within the context of the global life sciences cross-disciplinary integration industry built upon this foundation, the opportunities seem boundless.

In addition to the strong confidence in technical selection and precise judgment of industry development, LinkZill draws strength from the extensive expertise accumulated over its five-year history in the TFT domain, along with outstanding delivery capabilities. Currently, LinkZill has provided TFT chip development and delivery services to over a hundred global clients, with a cumulative production output exceeding 150,000 units, and approximately 30% of its revenue coming from overseas markets.

Crucially, the synergy between semiconductor and life sciences technologies and talents at LinkZill operates in a "bidirectional journey." Yin Le (Emma), partner of ZhenFund, whom invested in LinkZill for two consecutive rounds, said to 36Kr, "LinkZill has assembled an extremely adaptive and open-minded team. When such a group comes together, they have the ability to traverse cycles and head towards limitless possibilities, we believe LinkZill's furture will go a long way."

It is evident that the favorable timing (reaching a crucial juncture in improving life science efficiency), geographic advantages (China's TFT industry chain and technological strengths), and the harmonious collaboration of people (a cross-disciplinary innovative team) are in place.

The core challenge ahead lies in perfecting the design of the toolchain, making sound technical selections, overcoming R&D obstacles, and bridging the gap in the business cycle – these are the key factors that will determine the success of the venture.

Embracing the Emergence of AI and Continuing Global Advancement

In the history of the technology industry, every step of innovation must meet the needs of a specific scenario, and the cross-fertilization of semiconductors and life sciences is no exception.

Looking back over the past few years, the capabilities of AI have experienced explosive growth, particularly in areas such as AI-assisted design of nucleic acids and protein sequences, as well as predicting molecular interactions, showcasing tremendous capabilities.

"At this stage, however, AI can only provide predictive models and cannot offer verified results. The AI model itself needs iteration through a substantial amount of experimental data. Therefore, even though AI provides us with strong 'design' capabilities, we still need to concurrently construct hundreds of sequences, even build thousands of mutants, undergo numerous rounds of directed evolution, and collect tens of thousands of data points to screen out those sequences that truly industrialize or become viable drugs," Dr. Kang Kang, Partner and Chief Bio-informatics Officer at LinkZill, told 36Kr.

Hence, to harness the emerging design capabilities of AI and carry out thousands of parallel and sequential experiments, it is imperative to integrate the high-throughput construction of reaction systems, precise parallel control of reaction processes, and real-time sensing of reaction results into a single device. This achieves a high degree of integration and automation, minimizing manual intervention. Additionally, it is essential to conduct these experiments on a large scale under microfluidic systems to significantly reduce reagent and consumable costs. By incorporating AI design capabilities in the laboratory, accumulating more standardized data, continuously iterating AI models, and accelerating the research and development cycle, LinkZill aims to truly embrace the benefits of AI for Science.

LinkZill is precisely engaged in such endeavors. The introduction of the TFT-DNA Benchtop Synthesizer represents the first tool utilizing TFT semiconductor technology to address cost and manpower bottlenecks in life science research and development. The commercial cycle has received initial validation.

36Kr observed that in 2022, the global DNA synthesis service market will be about $6.4 billion , of which the Chinese DNA synthesis service market will be about RMB 3 billion.

"Based on LinkZill's life science product line layout, we have achieved several strategic collaborations and intentions in various areas, including oligonucleotide libraries, gene libraries, integrated serial experimental tools, AI-assisted nucleic acid and protein design and screening, mRNA drugs and modular antigen vaccines, capture sequencing, miniaturized NGS library construction, in situ spatial organization, and many more," revealed Dr. Kang Kang. He emphasized that LinkZill's ultimate goal is to build a fully integrated toolchain, serving synthetic biology, innovative drug development, sequencing library construction, and point-of-care testing (POCT).

With the goal of integrating tools for the entire life sciences process, LinkZill also pays special attention to the completeness of the toolchain and supporting solutions.

High-throughput DNA synthesis technology has been developed for two decades, but due to the existing technology selection, technical parameters and the innovation model of "single link breakthrough", there are still limitations in mature downstream application scenarios.

"Whether it's gene splicing using products from high-throughput DNA synthesis or conducting high-throughput screening, the upstream design threshold and the downstream manpower bottleneck are both very apparent. Taking large-scale gene synthesis as an example, we aim for our toolchain to cover the entire process from gene sequence design, synthesis, splicing, sequence verification, to product screening. The goal is to reduce the difficulty of using the entire toolchain, eliminating the ubiquitous design thresholds, manpower bottlenecks, cost bottlenecks, and delivery cycle bottlenecks that were prevalent throughout the entire workflow," added Dr. Kang Kang.

LinkZill's ambition to enter the field of biosemiconductors goes beyond this. It is launching a global impact with a vision and ambition for globalization.

"Globalization has never been a question mark in my mind; it is a must-to-do thing," expressed by Dr. Linrun Feng. LinkZill has set up a marketing center in Cambridge, UK, this year, while a research and development center is also in the planning stage.

Next, LinkZill aims to increase the proportion of overseas business to 50% within the next two years, and continue to promote the globalization process.

Relying on China's strong and mature TFT semiconductor manufacturing industry, LinkZill is also looking forward to forming a close community of destiny with China's industrial development as it explores cross-industrialization opportunities in the global life sciences. "Rooted in China, it is extremely valuable to bring products polished with China's industrial chain to the global market to solve global problems." Dr. Linrun Feng said.

Undoubtedly, starting from China and expanding globally, the industrialization of cutting-edge cross-disciplinary technologies is scripting the story of Chinese enterprises.

There is no doubt that the industrialization of cutting-edge cross-cutting technologies is writing the story of Chinese enterprises, starting from China to global layout.

Deepening into life sciences: Initiating a New Paradigm Shift

Innovation often requires a group of daring individuals, and as the team represented by LinkZill strives, the TFT semiconductor in the field of life sciences may usher in a new paradigm shift, bringing enormous possibilities for the industry's future development.

Regarding the future development of the industry, Dr. Linrun Feng believes that semiconductors will be ubiquitous in the field of life sciences, so that people anywhere in the world can benefit - whether it is the detection of viruses in the African region, or people concerned about environmental monitoring and other areas, can be greatly improved. Every entrant will also enjoy the dividends of the industry's development.

"My motivation is to use technology to help as many people as possible. From the very beginning of the business, the vision of LinkZill has been 'Linking zillions of people and technology. Linking zillions of hearts with love,'" Dr. Linrun Feng stated. "Our goal is to build a bridge between TFT semiconductor and the field of life sciences, and as we expand and strengthen this bridge, so the 'traffic' and flow of information between the two sides will increase. Industry barriers will gradually dissolve, leading to a remarkable explosion of synergy between the two."

As the saying goes, "The wide sea allows the fish to leap about and the vast sky the birds to fly." Just like in the past two decades, the interdisciplinary innovation of computer science, biotechnology, materials science, and other disciplines has continuously given birth to revolutionary products such as surgical robots and artificial hearts, creating immense value. In the innovative journey of cross-border integration between semiconductors and life sciences, participants will continue to iterate and extend infinitely, bringing infinite imagination to the industry.

"With the unwavering belief that what you're doing is in the right direction, all that's left to do is to throw yourself into it." At the end of the interview, Dr. Feng Linrun said.