Breaking the Deadlock: Suzhou Wiki Genomics Solves Multiple Bottlenecks in Domestic Nucleic Acid Mass Spectrometry Reagents, Accelerating Clinical Adoption
Targeted therapies and immunotherapies have crafted an anti-cancer myth with unprecedented precision, bringing precision medicine gradually into the public eye. How to achieve precise medication? The answer lies in precision diagnosis; only by determining the molecular subtype can targeted treatment be administered. Today, precision diagnosis has become an indispensable testing component throughout the entire course of medication.
As technology continues to evolve, precision diagnostics has progressed from traditional histological and immunohistochemical diagnoses to molecular diagnostics. Molecular diagnostics enables physicians to classify patients with the same disease in a clinically meaningful way, thereby identifying specific disease subtypes that are sensitive to particular treatments and therapeutic agents.
According to an analytical report released by Market Research Online, the size of China’s molecular diagnostics market reached USD 1.762 billion in 2018, representing a year-on-year growth of 14.1%. By 2025, the market size is projected to reach USD 4.243 billion, with total revenue increasing by more than 137% year-on-year.
Policy support and growing capital attention are accelerating the development of the molecular diagnostics industry, with continuous improvements in the precision and accuracy of molecular diagnostics. Currently, common molecular diagnostic technologies mainly include quantitative real-time PCR (qPCR) and next-generation sequencing (NGS). With the advancement of MALDI-TOF-MS technology, nucleic acid mass spectrometry has also emerged.
Nucleic acid mass spectrometry enables the simultaneous detection of dozens to hundreds of targets in a single sample, with a daily throughput exceeding 1,000 samples. Furthermore, result analysis is straightforward, eliminating the need for professional interpretation of reports. The emergence of nucleic acid mass spectrometry addresses the limitations of qPCR (low throughput) and NGS (long turnaround time and complex report interpretation). It has become an effective detection method for studying single nucleotide polymorphisms (SNPs), gene insertions/deletions, alternative splicing, copy number variations, gene expression, genomic DNA methylation, and post-transcriptional modifications of tRNA and rRNA.
In the field of nucleic acid mass spectrometry, VCBeat has recently taken notice of Suzhou VigiGene Technology Co., Ltd. (hereinafter referred to as “Suzhou VigiGene”), an innovative company founded in 2022.Suzhou Viki was co-founded by multiple senior medical doctors with extensive industry experience. Centered on its proprietary gene testing technologies, the company provides comprehensive nucleic acid mass spectrometry solutions for diverse scenarios, including clinical and laboratory settings. These solutions encompass laboratory construction, instrumentation, test panel selection, reagent development, and end-to-end clinical testing services. As a next-generation genetic testing institution, Suzhou Viki is committed to delivering highly stable and cost-effective testing services by developing more economical, scientifically robust, and highly sensitive detection methods.
The emergence of MALDI-TOF-MS technology in the 1980s broke with the traditional limitation of mass spectrometry to small-molecule analysis, enabling the study of biological macromolecules such as nucleic acids and proteins by mass spectrometry. This advancement has greatly propelled the development of genomics and proteomics, bringing revolutionary breakthroughs to the fields of biology and medicine.
Nucleic acid mass spectrometry is a multiplex PCR analytical detection system developed based on MALDI-TOF-MS technology. By leveraging the technical approach of “multiplex PCR + high-throughput chip + time-of-flight mass spectrometry,” it enables simultaneous multi-gene, multi-locus detection with high throughput and rapid analysis, while maintaining high sensitivity and specificity, and offering exceptional cost-effectiveness.
In genetic testing, common molecular diagnostic techniques include qPCR and NGS. Due to the limitation on the number of fluorescence channels in qPCR assays, achieving higher throughput relies on repeated testing; meanwhile, NGS-based analysis incurs higher costs and has a report turnaround time of up to seven days. “For clinical needs, when the number of target loci ranges from 20–30 or is within 100, nucleic acid mass spectrometry is a more suitable detection technology,” said Lin Yousheng, co-founder of Suzhou Weiji.
Mass spectrometry of nucleic acids enables direct detection based on differences in molecular weight. When genetic variations occur in nucleic acids, whether through base substitutions or modifications, the molecular mass of the DNA is altered. Therefore, precise identification can be achieved as long as the molecular weights of the amplified target sequences differ.
Nucleic acid mass spectrometry is suitable for genetic testing of 10–100 target loci, demonstrating over 99% concordance with Sanger sequencing and excellent reproducibility. Reportedly, the instruments and associated reagents for nucleic acid mass spectrometry are relatively low-cost. The system can analyze 50 loci per well and process 96 samples in a single run. Each test takes 8 hours, with a report turnaround time of approximately 3 days.
In 2018, the Chinese Expert Consensus Collaboration Group on Medical Applications of Nucleic Acid Mass Spectrometry published the “Expert Consensus on the Application of Nucleic Acid Mass Spectrometry in China” in the Chinese Medical Journal. This document systematically introduced the principles and applications of MALDI-TOF-MS technology, aiming to enhance awareness of nucleic acid mass spectrometry in clinical and laboratory settings across China and to promote its translational clinical application. Currently, nucleic acid mass spectrometry is more suitable in clinical practice for diagnosing complex, multi-target diseases, primarily including genetic birth defects, oncology, pharmacogenomics, multiplex pathogen detection, and drug resistance testing.
Constrained by technical barriers and policy changes, domestic nucleic acid mass spectrometry reagents have long relied on imports. In addition to high costs, supply lead times and other factors have further hindered the clinical adoption of nucleic acid mass spectrometry technology. “The clinical application of nucleic acid mass spectrometry requires attention to multiple aspects, including the sensitivity, specificity, throughput, turnaround time, and cost of the technical platform,” said Lin Yousheng.
To achieve the localization of nucleic acid mass spectrometry reagents, Suzhou Weiji has optimized multiple steps in the nucleic acid mass spectrometry detection process. PCR technology is one of the key technical components of nucleic acid mass spectrometry. By employing LNA-Blocker technology, Suzhou Weiji suppresses negative templates to improve detection rates. Additionally, leveraging its independently developed multiplex PCR design software, the company has designed UEP primers with high specificity, enabling the amplification of more than 100 primer pairs.
Nucleic acid mass spectrometry primarily determines test results by detecting the products of multiplex PCR reactions, specifically the mass of single-base extension products. Currently, nucleic acid mass spectrometry technology mainly relies on single-base extension reactions for operation. The efficiency of single-base extension affects the detection efficiency of nucleic acid mass spectrometry, while resolution is a critical criterion for successful detection.
dNTP modification technology is a critical technique in the single-base extension process. Currently, among the mature nucleic acid mass spectrometry reagents available on the Chinese market, the minimum molecular weight difference of dNTPs is 9.21 Da. During detection, due to this small molecular weight difference, the resolution between different peak regions is very low when detecting SNPs with A>T mutations. Additionally, significant differences in peak heights can lead to phenomena such as “bulging peaks,” which interfere with result interpretation. This has become one of the technical bottlenecks restricting the clinical application of nucleic acid mass spectrometry.
Based on its years of technical development experience, Suzhou Weiji has mastered the dNTP modification technology for nucleic acid mass spectrometry.According to reports, the modified dNTPs exhibit effective single-base termination and demonstrate exceptionally high ligation efficiency. Furthermore, this modification results in a molecular weight difference greater than 15 Da, providing high discrimination and reducing the risk of failure.
In response to diverse testing scenarios, Suzhou Weiji has also made technical advancements and implemented solutions, dedicating itself to expanding the clinical application of nucleic acid mass spectrometry. For instance, by establishing an anti-contamination protocol for methylation-specific nucleic acid mass spectrometry assays, PCR product contamination can be reduced by 98%. This approach resolves the industrialization challenge of inaccurate results caused by PCR product contamination in DNA methylation testing, without compromising assay sensitivity.
Furthermore, leveraging the core team’s years of deep expertise in the testing industry, Suzhou Weiji has accumulated ctDNA gene mutation profiles, DNA methylation profiles, SNC, CNV, and MSI data from tens of thousands of tumor samples; whole-genome sequencing data from tens of thousands of tumor samples; and data on ctDNA content, fragment size, breakpoints, GC-rich regions, and other parameters from tens of thousands of tumor samples. This extensive dataset lays a solid foundation for further technological optimization and product development.
By implementing technical optimizations across multiple stages of the nucleic acid mass spectrometry testing workflow, Suzhou Vigi plans to develop three solutions under the Laboratory Developed Tests (LDT) model, tailored to clinical use scenarios:Pathogenic Microorganism Genetic Testing, Pharmacogenomic Testing (Genetic Testing), and Tumor Genetic Testing。
Pathogenic microorganism genetic testing will cover over 91% of respiratory infectious diseases by developing a combined detection kit for 39 types of pathogens. Pharmacogenomic testing will encompass medication-related genetic testing for cardiovascular and cerebrovascular diseases, autoimmune disorders, psychiatric conditions, and infectious diseases, as well as pathogenic gene testing for monogenic hereditary diseases, thereby enhancing the safety and efficacy of pharmacotherapy across various disease categories. In the field of tumor genetic testing, Suzhou VGI is currently focusing on plasma cell-free DNA methylation detection for gastrointestinal cancer screening, aiming to map the methylation profiles of CpG islands in the promoter regions of plasma cell-free DNA.
Currently, Suzhou Weiji has developed domestically produced reagents for whole blood/swab nucleic acid purification, plasma cell-free DNA purification, multiplex PCR amplification, single-base primer extension, and cationic purification of PCR products, as well as two software programs: a multiplex PCR design program and a UEP primer design program. It can be said that Suzhou Weiji has successfully established the complete technological chain for nucleic acid mass spectrometry.
According to the introduction,"MASS GEL," a universal reagent for nucleic acid mass spectrometry developed by Suzhou WeijiTM"Compatible with commonly available nucleic acid mass spectrometers on the market.". "In terms of conversion rate, amplification efficiency, yield, stability, and operational steps, MASS GEL TM“The performance was outstanding, with a conversion rate exceeding 98% and the experimental procedure streamlined to just five steps,” said Lin Yousheng.
“With the rapid development of domestic nucleic acid mass spectrometry, the costs of instruments and reagents have continued to decline, approaching those of qPCR instruments and reagents, thereby demonstrating a clear cost advantage. From both technical and cost perspectives, nucleic acid mass spectrometry has the potential and opportunity to play a significant role in clinical applications,” emphasized Lin Yousheng.