10K Genomics Advances High-Throughput Single-Cell Multi-Omics Sequencing with Droplet Microfluidics Technology
On February 12, 2001, scientists from the six countries participating in the Human Genome Project released a high-precision map of the large-scale sequencing of DNA across the 23 pairs of human chromosomes. This marked humanity’s first exploration of the mysteries of life from a molecular perspective, and this research, hailed as the “Moonshot” of life sciences, became a foundational force driving the development of precision medicine. In the period that followed, a vast number of genetic testing companies, including BGI Genomics, emerged, generating massive amounts of microscopic human data. However, as understanding of diseases has deepened, data obtained through bulk multi-cell sequencing can no longer meet the granularity required for diagnosing certain complex diseases.
In October 2016, the Human Cell Atlas (HCA) initiative was launched in London, United Kingdom, by leading scientists worldwide. This initiative aims to determine the unique identity of each cell type among the 40 trillion cells in the human body and to construct a three-dimensional map of the human genome based on intercellular collaborative pathways. Single-cell sequencing technology serves as a critical foundational technology for the implementation of the HCA initiative.
Unlike traditional sequencing methods that provide averaged omics data based on large populations of cells, single-cell sequencing can obtain comprehensive omics data for every individual cell within a sample, clearly identify the cell types present, and record specific changes occurring in each cell. Therefore, the revolutionary significance of single-cell technology in biomedicine is comparable to the invention of the microscope, as both enable researchers to truly observe the subtle differences among individual cells.
Professor Shi Weiyang began researching single-cell sequencing technology in 2015, just six years after the technique was first applied to embryonic cell studies. Professor Shi told VCBeat that although single-cell sequencing has moved beyond its earliest phase, which relied entirely on manual operations, even automated single-cell sequencing remains a highly technically demanding endeavor.
“At present, single-cell sequencing cannot be operated by researchers after only simple training, but there is indeed a rigid demand for this technology in scientific research and clinical practice.” Enabling more researchers to utilize single-cell sequencing technology and accelerating its standardization is precisely the original intention behind Professor Shi Weiyang’s founding of Wancheng Genomics.
In February 2018, after years of teaching at Tongji University and Ocean University of China, Professor Shi Weiyang, having amassed extensive experience in the cutting-edge applications of single-cell sequencing technology, decided to become a pioneer in promoting this technology within China. Subsequently, Professor Shi joined forces with Mr. Wu Ziniu, his former classmate from the Department of Biological Sciences at Tsinghua University, to establish Wancheng Jingwei Gene Technology (Beijing) Co., Ltd. (abbreviated as Wancheng Genomics) in Beijing. The company is dedicated to advancing the standardization and productization of high-throughput single-cell multi-omics sequencing technologies, providing customers with stable and reliable single-cell sequencing services.
In January, one year after its establishment, Wancheng Genomics secured a RMB 5 million angel round of financing from Heli Investment. The company subsequently rapidly commissioned a new laboratory and launched a variety of single-cell omics services. Professor Shi told VCBeat that, without proactive market outreach in the early stages, the company had already served nearly 30 clients across China, including hospitals, research institutions, sequencing companies, and industrial enterprises.
Currently, Wancheng Genomics provides scientific research services externally and meets the biological research needs of clinical departments. In addition, the prototype of the microfluidic device independently designed by Wancheng Genomics has been completed and will be gradually made available to users, with continuous improvements being made to meet mass production standards.
Professor Shi Weiyang believes that personalized diagnosis and treatment targeting diseased cells directly, enabled by single-cell sequencing, represents an iteration of precision medicine based on individual genomic information, constituting Precision Medicine 2.0. Precision Medicine 2.0 posits that each disease in every individual is a unique entity; each patient’s clinical condition, disease progression, and corresponding cellular pathological types vary, leading to distinct therapeutic needs. Currently, single-cell sequencing is primarily applied in clinical settings for the precise diagnosis and treatment of complex diseases, including tumor immunotherapy.
The pathogenic mechanisms of complex diseases often involve multiple types of cellular pathology. Without an accurate understanding of the true causes at the cellular level, monotherapies typically affect only specific cell types, leaving many other cell types unresponsive, which significantly reduces drug efficacy. If comprehensive information from all cells could be obtained simultaneously, personalized treatment plans could be developed based on targeted diagnostics. According to Professor Shi, single-cell sequencing technology has already been applied in tumor immunotherapy, autoimmune diseases (such as multiple sclerosis), and complex neurological disorders (such as Alzheimer’s disease), enabling researchers to identify disease-specific lesions within individual cells.
Currently, the highly prominent field of tumor neoantigen therapy has emerged as a key direction for the early integration of single-cell sequencing technology with clinical applications. Tumor neoantigen therapy represents a purely personalized treatment approach, as each individual’s tumor harbors specific antigens. Researchers predict these neoantigens and develop targeted therapies accordingly. The detection of neoantigen presence and antigenicity is based on DNA rather than gene expression; therefore, single-cell sequencing is required to determine the expression levels of neoantigens, thereby enabling rapid screening. According to Professor Shi, Wancheng Genomics is collaborating with multiple companies specializing in neoantigen research to explore the use of single-cell sequencing as a tool to verify whether the predicted antigens are expressed in individual tumor cells.
However, due to the numerous bottlenecks inherent in single-cell sequencing technology itself, as well as its high cost, time-consuming nature, and operational complexity, it cannot yet replace bulk-cell sequencing on a large scale. “Single-cell sequencing will only be adopted in more research and analytical applications once it achieves convenience and cost-effectiveness comparable to those of bulk-cell sequencing.”
Placing a single cell into a channel and performing a series of operations, including labeling, library preparation, and sequencing, to obtain the omics information of that cell constitutes a simplified single-cell sequencing workflow. Among these steps, labeling and library preparation largely determine the sequencing throughput. Scientists have employed various methods to label large numbers of single cells, aiming to assign a unique index to each cell. This index is a segment of barcode DNA that can be read during sequencing, thereby allowing each read to be individually assigned to a specific single cell and enabling the distinct reading of single-cell data.
In 2015, droplet microfluidics and microwell plates, the two currently mainstream high-throughput single-cell sequencing labeling and library preparation technologies, emerged almost simultaneously. In China, most early-stage companies engaged in single-cell sequencing research adopted the microwell plate labeling approach. However, since microwell plate technology can only isolate cells, high-throughput single-cell technologies based on this platform are limited to transcriptome sequencing and have no other omics applications. Vantron Bio chose the more scalable droplet microfluidics approach, with its core technology enabling the labeling, measurement, and evaluation of large numbers of individual cells within microdroplets.
The primary bottleneck of current high-throughput single-cell sequencing technologies on the market is their reliance on a single omics approach, limiting their application to only a few types of omics. Professor Shi Weiyang told VCBeat that WanCheng Genomics aims to develop single-cell sequencing technologies for all omics disciplines, ultimately achieving the simultaneous measurement of multiple omics profiles within individual cells in a single assay.
Currently, Wancheng Genomics has achieved high-throughput single-cell sequencing for transcriptomics, genomics, ATAC, methylation, ChIP, proteomics, and immunology. Compared to 10x Genomics, the U.S. benchmark company in single-cell sequencing, Wancheng Genomics demonstrates superior performance in genomic, methylation, ChIP, and proteomic sequencing.
At this stage, Wancheng Genomics provides both scientific research services and upstream instruments and reagents. Professor Shi Weiyang stated that before single-cell sequencing technology can be effectively utilized by all, professional companies must offer specialized sequencing services. However, the true goal pursued by Wancheng Genomics is to provide standardized high-throughput single-cell multi-omics sequencing products. Professor Shi Weiyang told VCBeat that Wancheng Genomics’ vision is to become a top-tier technology provider.
It is reported that Wancheng Gene is currently conducting its Series B financing round, with a target amount of RMB 20–30 million. The funds will be primarily used for the development of new omics products and market expansion. Professor Shi Weiyang stated that while Wancheng Gene plans to expand its influence in China’s large-scale scientific research services market, it intends to launch single-cell epigenomic sequencing products, including ATAC-seq and methylation assays, within this year. Additionally, the company will introduce immune repertoire sequencing solutions tailored for clinical and industrial applications, such as immunotherapy and antibody development.
Furthermore, Wancheng Genomics will launch the “Tumor Multi-Omics Initiative,” recruiting 20 researchers at the forefront of oncology therapeutics to conduct in-depth clinical research collaborations using high-throughput single-cell multi-omics technologies.