Shanghai Jiao Tong University Licenses Exosome Subtype Detection Technology for RMB 1.5 Million Plus Equity
Recently, the Advanced Industrial Technology Research Institute of Shanghai Jiao Tong University released a public notice on the conversion of scientific and technological achievements, proposing to“Invention Patent: A Single-Particle Imaging-Based Method for Exosome Subtype Analysis”, with“Transaction amount of RMB 1.5 million in cash + the cash value corresponding to a 1% equity stake,”Conversion is carried out through “implementation by the inventors.”
The assignee of this patent conversion is the inventor of the patent, an Associate Professor at the School of Biomedical Engineering, Shanghai Jiao Tong University.Afterglow. Professor Yu Hui received his Ph.D. in 2011 from the College of Biomedical Engineering at Zhejiang University. He subsequently conducted postdoctoral research and served as an Assistant Research Scientist at the Hong Kong University of Science and Technology, Nanjing University, and Arizona State University in the United States. In 2017, he returned to China to establish his independent research career. His primary research interests focus on optical biosensing technologies and instrumentation. Over the past five years, he has published multiple papers as the corresponding author in prestigious journals such as PNAS and ACS Nano, and has served as a key investigator in a Major National Natural Science Foundation project for the development of major scientific instruments.
The core patent of the transaction focuses on separation-free, precise analysis of exosome subtypes. This patent utilizesConstruct an integrated system of “high-specificity sensing chips + high-sensitivity imaging monitoring + rapid data analysis”, enabling separation-free detection of exosome subtypes while simultaneously acquiring particle size and surface marker information. It combines the advantages of ease of operation, high sensitivity, and high specificity, is suitable for clinical scenarios such as cancer liquid biopsy, and effectively breaks through the bottlenecks of traditional technologies.
Liquid biopsy technology, which detects circulating biomarkers in the blood, aims to enable early cancer screening, guide treatment strategies, monitor therapeutic response, and detect recurrence, making it one of the most promising tools for cancer diagnosis and treatment today.
Exosomes are small membrane-bound vesicles, with diameters ranging from 30 to 150 nanometers, secreted by cells. They are widely present in various human body fluids, including urine, blood, breast milk, and saliva. Exosomes contain proteins, lipids, and nucleic acids specific to their host cells and can act as signaling molecules to transmit information to other cells, thereby modulating their functions. Exosomes play critical roles in numerous physiological and pathological processes, such as antigen presentation during immune responses, tumor growth and metastasis, and tissue repair following injury.
Exosomes secreted by different cell types vary in composition and function, making them suitable as biomarkers for liquid biopsy. Compared with other circulating biomarkers, exosomes offer unique advantages, including ease of enrichment, high stability, and resistance to degradation, thereby attracting increasing attention.
Due to the diversity of tumor types, heterogeneity of tumor mutations, varied cellular origins, and differences in the extracellular environment, circulating exosomes exhibit significant inter-individual variability in terms of size distribution, quantity, and cargo composition.By employing asymmetric flow field-flow fractionation, the 30–150 nm exosome population can be further subdivided into three subpopulations: <50 nm, 60–80 nm, and 90–120 nm.Mass spectrometry analysis revealed that each subpopulation possesses unique characteristic biomarkers. This strongly indicates a specific correlation between exosome size and their cargo content.
Due to variations in cancer types, there is a correlation between the cancer-specific markers carried by exosomes secreted by cancer cells and their particle size. Currently, liquid biopsy techniques based on bulk exosome analysis, such as thermophoretic enrichment combined with aptamer-based fluorescent multiparametric detection, exhibit low accuracy in diagnosing six common types of cancer.
Therefore,Development of Analytical Methods for Exosome Subtypes Based on Particle Size and Surface Markers, which is of paramount importance for the precise diagnosis of cancer. Currently, technical approaches for exosome analysis include: observing exosome size and morphology using transmission electron microscopy (TEM), estimating average particle size via dynamic light scattering (DLS), and detecting protein biomarkers through methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA). However, the entire analytical workflow is not only cumbersome, time-consuming, and sample-intensive due to complex processing steps, but also fails to account for heterogeneity among individual exosomes, thereby precluding the simultaneous acquisition of integrated information on both particle size and molecular biomarkers.
Professor Yan Xiaomei’s Research Group, Xiamen UniversityIn the field of NanoFCM technology, remarkable achievements have been made, successfully enabling high-sensitivity measurement of 40 nm exosomes. However, due to the lack of sufficient molecular information, this technique relies on fluorescent immunolabeling of exosome samples to achieve specific detection. This process is constrained by multiple factors, including the number of fluorescence channels, fluorescence analysis emission efficiency, sample pre-processing, and semi-quantitative detection, resulting in significant limitations in exosome subtype analysis.
Conventional surface plasmon resonance (SPR) technology lacks the capability for single-particle imaging analysis, making it impossible to simultaneously obtain information on exosome particle size and molecular biomarkers, and even more challenging to analyze exosome subtypes. Methods that classify exosome populations by particle size using asymmetric flow field-flow fractionation or size-exclusion chromatography are highly inconvenient for clinical applications due to their stringent technical requirements.
In response to the aforementioned technical pain points, the team aims to leverage an innovative technological framework to address challenges in exosome subtype analysis“Difficult separation, limited information, complex operation, and low accuracy”...core issues, providing a more efficient technical solution for liquid biopsy in cancer. The team overcame the difficulty inherent in existing technologies, which require further separation of exosomes by particle size, and developed a separation-free method for analyzing exosome subtypes at the single-exosome level, characterized by high sensitivity, high specificity, and ease of operation.
This method achieves precise subtype classification by performing dynamic imaging and digital analysis of individual exosome particles, simultaneously acquiring information on particle size and surface molecular markers, and leveraging data analysis algorithms. This approach effectively addresses the challenge of difficult subtype sample separation in exosome subtype analysis.
1. Breakthrough in the "separation dependency" bottleneck, achieving efficient separation-free analysis
Addressing the core challenge of traditional techniques that rely on complex methods such as asymmetric flow field-flow fractionation and size-exclusion chromatography to separate exosome subtypes, this patent establishes an integrated “sensor chip–imaging monitoring–data analysis” workflow. Microfluidic chips modified with nucleic acid aptamers are used to capture exosomes, while a surface plasmon resonance imaging platform enables real-time monitoring. Coupled with a Python-based image analysis system, this approach simultaneously extracts particle size and surface marker information, allowing cluster analysis to be performed without prior subtype separation. This workflow significantly simplifies operational procedures, shortens detection time, and effectively overcomes the barriers of “difficult separation and time-consuming processes” in clinical applications.
2. Combines high sensitivity with high specificity, significantly improving detection accuracy
In terms of detection performance, this patent has achieved a "dual-high" breakthrough:On one hand, by employing a surface plasmon resonance imaging (SPRi) platform equipped with oil immersion objectives having a numerical aperture of 1.39–1.79, p-polarized lasers with a wavelength range of 550–780 nm, and high-resolution CMOS cameras, the system achieves a detection sensitivity as high as 5×10^7 exosomes/mL. It is capable of detecting exosomes across the full size range of 30–150 nm, with performance approaching that of nanoparticle tracking analysis (NTA). On the other hand, thiolated nucleic acid aptamers self-assembled via Au-S bonds serve as recognition elements; these aptamers can be precisely selected according to the specific disease type being tested. Meanwhile, remaining active sites on the chip surface are blocked using mercaptohexanol (MCH) and bovine serum albumin (BSA), which effectively reduces non-specific adsorption, significantly enhances the specific capture capability for target exosomes, and minimizes interference signals.
3. Aligned with Clinical and Industrialization Needs, Featuring Prominent Practical Value
From the perspective of practical implementation, this patent demonstrates significant utility:First, the chip fabrication process is simplified; PDMS channels can be prepared through conventional steps such as photolithography and high-temperature curing, while the bonding and modification processes are easily standardized, offering strong operability and excellent reproducibility. Second, data analysis is efficient and convenient: image differencing and tracking algorithms based on the Python platform can rapidly process data, enabling single-particle counting and particle size statistics without requiring complex professional operations. Furthermore, this technology is well-suited for liquid biopsy applications, allowing direct detection of bodily fluid samples such as blood with minimal sample pretreatment. It provides precise data support for cancer type identification and early screening, demonstrating significant potential for industrialization and clinical translation.
As a core technological direction in liquid biopsy and precision medicine, exosome subtype analysis has given rise to a cohort of domestic and international enterprises focused on this field, covering the entire value chain including technology R&D, product supply, and testing services:
Exosome AnalyticsLeveraging the French Genopole Campus“Shaker Program”Its technological achievements have been established, with headquarters in Evry and Elena Khomyakova serving as CEO. The company is dedicated to researching and developing technologies and products capable of highly sensitive analysis of protein markers on the surface of extracellular vesicles. Leveraging these technologies, the company is developing a diagnostic platform that enables early cancer detection and tumor subtyping by analyzing histological markers on extracellular vesicles.
Exosome DiagnosticsIt was a benchmark enterprise in the field of exosome diagnostics in the United States, later acquired by Bio-Techne, and now serves as its core business segment, focusing on the detection of exosomal molecular biomarkers and therapeutic monitoring.
Exosome Diagnostics was founded by Dr. Johan Skog in 2008. Prior to this, Dr. Skog discovered that exosomes carry RNA biomarkers suitable for diagnostic purposes and recognized their role as “super communicators” in intercellular communication within the human body—two pivotal discoveries that served as the key impetus for establishing the company. Over the past decade, the field of exosome research has experienced rapid growth, with Exosome Diagnostics consistently remaining at the forefront and successfully developing the world’s first exosome-based liquid biopsy testing technology. As a leader in exosome technology, the company currently holds more than 250 patents.
Enze KangtaiAs one of the earliest companies in China to strategically position itself in the exosome sector, the company has established an Exosome Multi-omics Analysis Platform (Exoomics®), an Engineered Exosome Platform (Echosome®), and a Large-scale Exosome Production Platform (EchoPharm®), covering the entire value chain from exosome “cognition” and “engineering” to industrial “application.” Currently, the company collaborates with over 1,000 hospitals, research institutions, and enterprises both domestically and internationally, supporting the publication of more than 300 academic papers on exosomes, and has become a benchmark for exosome quality analysis and clinical translation.
Dolai BiotechIt is a biotechnology company based in Wuhan Optics Valley, co-founded by scientists and industry experts in the field of exosomes. Its core capabilities span an integrated “instrument–reagent–service” platform for exosome subtype analysis. The company’s independently developed “Fully Automated Exosome Extraction and Purification System” offers both micro-sample separation and large-scale preparation capabilities.
From R&D to industrial implementation, exosome subtype analysis has become a key link connecting basic research and clinical diagnosis, thanks to its unique value in the field of liquid biopsy.International companies such as Exosome Diagnostics have set industry benchmarks in patent portfolio development and clinical translation, leveraging their first-mover advantage. Their isolation and detection technologies, developed based on exosome stability, provide important references for the standardization of global exosome diagnostic products. Meanwhile, domestic enterprises are narrowing the gap with international advanced standards by building full-chain solutions, thereby accelerating the penetration of exosome subtype analysis from research services into clinical applications.
In the future, as detection sensitivity continues to improve, multi-omics data analysis capabilities are enhanced, and clinical validation data accumulate, exosome subtype analysis technology will play a greater role in scenarios such as early cancer screening, treatment monitoring, and prognosis assessment, injecting new momentum into the development of precision medicine. Whether through the technological leadership of international giants or the innovative breakthroughs of domestic enterprises, these efforts will jointly propel this field toward a new stage of development that is more efficient, more precise, and more accessible.