Will Organ-on-a-Chip Become the Next 'Chipped' Technology Vulnerable to Foreign Restrictions? How a Chinese Biotech Firm Is Pioneering Its Way into This Emerging Field

The development trajectories of organ-on-a-chip technology and high-throughput gene sequencing share certain similarities:In the preceding years, the gene sequencing industry had accumulated substantial expertise in technological innovation and clinical applications. It was not until this year, when Laboratory Developed Tests (LDTs) were included as pilot programs in the 14th Five-Year Plan, that the sector officially opened up.

“We follow a similar strategic logic—breaking through R&D barriers, establishing companies to facilitate the translation of scientific research, and clearly identifying customer needs before the organoid and organ-on-a-chip industries reach full maturity. This allows us to quickly seize first-mover advantage once the industry experiences explosive growth. This is also the rationale behind large CROs or pharmaceutical companies, such as WuXi AppTec, investing in organoid or organ-on-a-chip enterprises like Daxiang Technology at the angel round.”Dr. Chen Zongzheng, Founder and General Manager of Xirui Biotech, told VCBeat New Medicine.

Unlike most scientists and industry professionals with singular backgrounds, Chen Zongzheng not only brings over a decade of R&D experience in cell biology and organ-on-a-chip technologies, but has also served as an advisor to professional technology transfer companies, life and health industrial parks, and venture capital firms. He possesses a comprehensive and profound understanding of the biopharmaceutical industry and translational medicine, while having accumulated extensive industry resources.

In 2018, when the concepts and fields related to organoids and organ-on-a-chip had not yet gained attention in China, Chen Zongzheng already possessed a comprehensive understanding of the research and industrial development directions in this area. When venture capitalists were investing in Daxiang Technology, they sought his consultation. “I provided them with a detailed explanation of the concept and future prospects of organ-on-a-chip technology. In addition, I was actively engaged in popularizing knowledge about organ-on-a-chip through channels such as my Zhihu column and WeChat official accounts.”

In 2020, Xirui Bio was established in Shenzhen, focusing on the development of drug evaluation technologies and their applications based on complex in vitro microphysiological systems (organ-on-a-chip). Chen Zongzheng has also devoted more energy to the industrial translation of organ-on-a-chip technology.

In addition to Chen Zongzheng, who possesses comprehensive experience in scientific research and industrialization, other core members of the Xirui team also have extensive experience in related fields.

Dr. Wei Wenbo, Co-founder and Chief ScientistHe is a high-level talent in Shenzhen and a researcher at the BGI Research-Shenzhen Institute of Life Sciences, with over 10 years of experience in research and product development in the field of microfluidic chips, possessing strong capabilities in microfluidic development.

Furthermore, Professor Lin Bingcheng, a pioneering figure in Asian microfluidic chip technology, also serves as a strategic advisor to Xirui Biology.Professor Lin has been dedicated to research on capillary electrophoresis and microfluidic chip experiments since the 1990s, with a primary focus on biomedical and pharmaceutical applications. To date, Professor Lin has authored multiple books, including Laboratory on a Chip: Microfluidics, Organ-on-a-Chip, and Illustrated Guide to Microfluidic Chip Laboratories, and has applied for or holds more than 50 invention patents in the field of microfluidic chips.

To date, Xirui Bio has built a core, full-industry-chain team spanning interdisciplinary fields including materials science, engineering, cell biology, pharmaceutics, and artificial intelligence.

Against the backdrop of a professional team, Chen Zongzheng said, “As an entrepreneur in the highly challenging field of emerging technologies,I have defined another identity for myself: ‘Representative for the Popularization of Organ-on-a-Chip Concepts’."This role is akin to that of an industry science communicator; I aim to help more people and relevant departments correctly and comprehensively understand the concepts related to organ-on-a-chip technology, as well as its future development trends."

During his “promotion” of the author’s work, Chen Zongzheng also analyzed the current stage of organ-on-a-chip development in China. Citing the Technical Guidelines for Non-clinical Studies of Gene-Modified Cell Therapy Products (Trial), issued by the Center for Drug Evaluation (CDE) at the end of 2021, he pointed out that: “For gene-modified cell therapy products, when relevant animal models are unavailable, cell- and tissue-based models (such as two-dimensional or three-dimensional tissue models, organoids, and microfluidic models) may be used to provide useful supplementary information for the assessment of efficacy and safety.”

This indicates that current regulatory guidelines in China on gene and cell therapies position technologies such as organ-on-a-chip as “supplements” rather than core components. This aligns with the current stage of development of organ-on-a-chip technology. At present, organ-on-a-chip serves only to complement and augment existing technologies; “the new drug development process can still ‘survive’ without it, and it is not yet capable of effectively replacing model animals, particularly given the substantial market position that model animals have established in the new drug development industry.”

Chen Zongzheng explained that each model animal is an independent living organism, and its complexity cannot be fully simulated by current organ-on-a-chip technologies. With the advancement and refinement of organ-on-a-chip technology, simple model organisms such as zebrafish and nematodes may be rapidly replaced first, whereas replacing complex primate model animals will require prolonged development across the industry. Furthermore, from a temporal perspective, model animals have been used in pharmaceutical research and development for over half a century. The industry standards and regulations established around their use are relatively mature and comprehensive, making it difficult to achieve complete replacement in the short term.

From the debate over whether organ-on-a-chip technology can replace model animals, we should clearly recognize that:Despite the absence of organ-on-a-chip technology, new drug development can still proceed along its established trajectory. At China’s current stage of development, organ-on-a-chip technology is primarily intended to first replace simple model animals and to supplement existing disease animal models that are difficult to establish.

Chen Zongzheng believes that “organ-on-a-chip technology should currently serve as a complement to the limitations of existing disease models. As for replacement, that is a matter for the future. Whether and when such replacement will occur depends on how many scientists, engineers, pharmaceutical industry professionals, investors, and regulatory authorities collaborate to advance the organ-on-a-chip industry.”

Leveraging his prior experience and resource accumulation in the investment sector, Chen Zongzheng stated that he likely knows more pharmaceutical investors than most financial advisory (FA) firms. Despite this inherent advantage, Xirui Biotech has not aggressively pursued its fundraising efforts, standing in contrast to the current financing difficulties faced by many other startups.

“We want to wait, because we cannot remain mere proponents of a concept, nor can we simply keep talking about the concept and narrative of organ-on-a-chip technology. We need to present tangible outcomes, letting ‘facts and evidence’ speak for themselves. These achievements will also lend us greater persuasiveness and negotiating leverage in our collaborations with other upstream and downstream partners.”

Guided by the “down-to-earth” philosophy of focusing on delivering results rather than crafting narratives, Xirui Bio rapidly established its R&D center, production facility, and biobank around key milestones in the industrialization of organ-on-a-chip technology.

Its R&D center encompasses research and development and validation systems for organ-on-a-chip platforms and their peripheral power systems, as well as multiple organ-on-a-chip culture and drug evaluation systems. It is capable of supporting soft lithography-based (microfluidic) organ-on-a-chip design, small-scale fabrication, and functional validation; the development and establishment of microfluidic perfusion and pump-free systems; and the provision of drug evaluation services based on organoid-on-a-chip technologies. The production center enables the industrialization of microfluidic chips, including large-scale manufacturing and sterile packaging of chips made from various materials such as PS, PMMA, PC, PET, COC, COP, and ABS. The organoid biobank has collected nearly 150 cancer samples, providing human-derived cells for in vitro humanized tissue and organ biomimetic systems.

The successful establishment of these platforms hinges on Xirui Bio’s core competitive advantage: the Microphysiological Systems (Organ-on-a-Chip) Workstation.

Chen Zongzheng admitted, “When we first started our business, our ideas were relatively simple, such as developing basic organ-on-a-chip systems.”

However, Chen Zongzheng soon discovered that merely creating a standalone, simple organ-on-a-chip was not user-friendly for customers.“An organ-on-a-chip device, in isolation, does not resemble a commercial product; when integrated into the industrialized drug development process, it is susceptible to errors arising from various environmental factors and manual operations, thereby hindering the widespread adoption of organ-on-a-chip technology.”

To mitigate the impact of various errors, Xirui Bio has entered the organ-on-a-chip sector by focusing on standardized integrated workstations.

Furthermore, to address the bottlenecks in new drug development and the limitations of existing research models—such as limited techniques for acquiring drug response information incompatible with organ-on-a-chip platforms, the complexity of in vivo environments that are difficult to simulate, the high difficulty and cost of mass-producing organ chips, the lack of culture media supporting 3D cell cultivation, and the challenges in obtaining humanized cells with limited passage capacity—Xirui Bio has established platforms including information acquisition and intelligent analysis technologies for drug-induced cellular responses, microphysiological system simulation for organs/tissues, scalable organ chip manufacturing technologies, on-chip 3D cell culture technologies, and cell engineering technologies. These technologies are integrated into a one-stop organ-on-a-chip workstation.

Furthermore, organ-on-a-chip technology can fully leverage the advantages of multi-organ chip integration to evaluate ADME (absorption, distribution, metabolism, and excretion). This multi-organ chip enables the co-culture of cells from various key organs involved in ADME on a single platform, simulating in vivo ADME processes and facilitating drug efficacy and toxicity assessments that account for ADME factors using an organ-on-a-chip workstation.The use of such integrated multi-“organ-on-a-chip” systems in conjunction with workstations not only lowers the barrier to entry for organ-on-a-chip technology but also accelerates the pace of new drug development, thereby facilitating the rapid and straightforward adoption of organ-on-a-chip solutions by enterprises and promoting industry growth.

Backed by its technological platform, complementary team, and organ-on-a-chip workstations, Xirui Biology has established business segments in research consumables and instruments, clinical personalized precision medication guidance, and new drug R&D CRO services.

Based on its business segments, Xirui Bio has focused on technological directions such as 3D cell culture, organoids, and organ-on-a-chip platforms to research, develop, and manufacture standardized reagents, consumables, and instruments with industry consensus, initially aiming to meet the demands of the scientific research market. Subsequently, targeting hospitals and new drug R&D institutions, the company has developed a series of medical devices that fully leverage the standardization advantages of organ-on-a-chip technology and utilize patient-derived autologous cells. Additionally, it has established corresponding organ-on-a-chip-based solutions for existing new drug evaluation systems. Furthermore, Xirui Bio is actively collaborating with relevant institutions in less strictly regulated fields such as tobacco, environmental science, and cosmetics, helping them establish evaluation systems based on organ-on-a-chip technology.

Regarding the current development of organ-on-a-chip technology, in June and September of this year, the U.S. House of Representatives and Senate respectively passed the Food and Drug Amendments Act of 2022, formally incorporating organ-on-a-chip and microphysiological systems into non-clinical drug testing processes, thereby establishing their significant role as models for non-clinical research. Notably, the Act includes two key adjustments that have drawn considerable attention:

First, the revised bill uniformly amends “animal experiments” in the original bill to “non-clinical studies,” weakening the strong association in conventional understanding that equates “animal experiments” with “preclinical studies,” and provides a clear definition of “non-clinical studies.”

More importantly, the amended legislation, for the first time, incorporates organ-on-a-chip and microphysiological systems as an independent framework for non-clinical drug evaluation, recognizing them as research tools of equal importance to cell models, computer modeling, and animal models.

Regarding the introduction of the revised bill, Chen Zongzheng stated,Organ-on-a-chip technology risks becoming the next “chokepoint” technology subject to foreign containment. “There is currently a clear gap between China and other countries in the promotion and application of organ-on-a-chip platforms. Abroad, these systems have already been integrated into the same regulatory framework as animal testing and cell-based assays. In contrast, regulations issued in China this year merely designate organ-on-a-chip technology as a supplementary component of new drug development.”

Despite existing gaps, the industry as a whole remains in its early stages of development; both organ-on-a-chip and organoid technologies present challenges inherent to emerging fields, as well as opportunities characteristic of blue-ocean markets.

To accelerate its expansion into blue-ocean markets, Xirui Biotech has established close collaborations with dozens of universities, research institutes, and pharmaceutical companies, including Southern Medical University, Tsinghua University, Thermo Fisher Scientific, BGI, Shenzhen Second People's Hospital, and the Shenzhen Institute of Otolaryngology.

Looking ahead, Chen Zongzheng stated that Xirui Biotech will actively pursue financing to accelerate corporate growth. The company will also collaborate proactively with upstream and downstream partners in the industry to develop more reliable and user-friendly organ-on-a-chip models, expand its portfolio of application cases, and enhance industry stakeholders’ understanding of the organ-on-a-chip and organoid sectors, thereby jointly driving industrial advancement.