West China Hospital Licenses High-Efficiency Biological Sample Pretreatment Technology for Mass Spectrometry-Based Toxicology Diagnostics

On September 27, West China Hospital of Sichuan University issued an announcement proposing the transfer of a patent titled “A Pretreatment Method for Biological Samples.” The proposed transaction price is RMB 900,000 plus a 3% royalty on sales revenue. The transaction is currently in the public notice period, which will end on October 12.

The patents proposed for transfer in this transaction were invented by Peng Aihua, Cao Yu, and others. Both individuals have long been engaged in medical practice and scientific research in the field of acute poisoning, and have published numerous academic papers on the monitoring and treatment of acute poisoning. Notably, Cao Yu has been honored with titles such as “Sichuan Famous Physician” and “Academic Leader of Emergency Medicine in Sichuan Province,” and has published 87 academic papers as first author or corresponding author, including 41 SCI-indexed papers.

The patent proposed for transfer in this transaction, “A Pretreatment Method for Biological Samples,” is an invention patent applied in the field of precise diagnosis of acute poisoning.

According to "A Ten-Year Review and Prospects of Acute Poisoning Research in China," multiple regional epidemiological surveys indicate that acute poisoning cases account for approximately 2.7%–3.6% of emergency department visits during the same period, showing a year-on-year increase while the case fatality rate among acute poisoning patients remains persistently high.

Therefore, in-depth research into the clinical characteristics of acute poisoning and the improvement of diagnostic and therapeutic standards have become shared goals for stakeholders in the field of acute poisoning. In the pursuit of enhancing diagnostic and therapeutic capabilities, improving the efficiency of precise diagnosis has also become an essential imperative.

Currently, chromatography-mass spectrometry has become one of the most effective methods for rapid toxicological screening due to its combination of high separation capability from chromatography and high selectivity, specificity, and sensitivity based on mass-to-charge ratio detection in mass spectrometry. However, sample pretreatment is a necessary prerequisite for obtaining ideal chromatography-mass spectrometry analytical results.

However, existing methods for biological sample pretreatment fail to fully meet clinical demands. For instance, extraction methods are only suitable for compounds with low polarity and are not applicable to the detection of water-soluble compounds. Protein precipitation, in practical applications, is influenced by two factors: the binding affinity between the analyte and plasma proteins, and the solubility of the analyte in the organic solvent used. When the analyte binds tightly to plasma proteins or exhibits low solubility, sample pretreatment can result in the loss of the analyte.

As for solid-phase extraction (SPE) cartridges, the wide variety of sorbent types necessitates selection based on the properties of the target compounds, a process that is relatively complex and therefore unsuitable for broad-spectrum screening applications.

Against this backdrop, West China Hospital’s “A Pretreatment Method for Biological Samples” employs counter-current chromatography, leveraging differential partitioning of samples in a two-phase solvent system to achieve separation. By integrating multiple elution solvent systems, this approach provides a pretreatment method for biological samples that is suitable for broad-spectrum screening and offers high toxin recovery efficiency.

Specifically, countercurrent chromatography is a separation technique based on continuous liquid-liquid extraction, primarily applied to the separation and purification of natural products or synthetic compounds. Since countercurrent chromatography avoids solid stationary phases that may cause irreversible adsorption, it features high recovery rates, making it highly suitable for the pretreatment of natural biological samples.

In the patent specification, the team provides a detailed description of the method’s usage and notes that, compared with traditional biological sample pretreatment methods, the method disclosed in this patent can recover a wider variety of toxins, demonstrates broader applicability, and achieves a toxin recovery rate of over 65%.

After pretreatment, biological samples can proceed to the formal testing phase.

As previously mentioned, chromatography-mass spectrometry coupled techniques are currently the most widely applied technologies in the field of toxicology testing. The commonly used chromatography-mass spectrometry methods mainly include gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Among these, GC-MS is primarily suitable for volatile samples and is not applicable to non-volatile, highly polar, or thermally unstable compounds. In contrast, LC-MS is not subject to the aforementioned limitations and has a broader range of applications.

From a market perspective, according to the latest 17th edition of the Global IVD Industry Report released in the United States, the global clinical mass spectrometry market was valued at $930 million in 2024 and is projected to reach $1.435 billion by 2029. From 2024 to 2029, the clinical mass spectrometry market is expected to grow at a compound annual growth rate (CAGR) of 9%, making it the fastest-growing segment in the IVD field, second only to nucleic acid testing.

Among these, LC-MS is the most widely used type of clinical mass spectrometry. According to QYResearch estimates, LC-MS accounted for 76% of total sales in the clinical mass spectrometry market in 2018. Furthermore, due to the relatively high technical barriers associated with LC-MS, foreign giants such as Agilent, Thermo Fisher Scientific, and Danaher currently dominate the majority of the market share in this field.

Among these, Agilent’s liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems can be used for the qualitative or quantitative detection of analytes in human-derived biological samples, such as whole blood, plasma, serum, and urine, including endogenous substances (e.g., vitamins, amino acids, and hormones) and exogenous substances (e.g., therapeutic drugs).

Danaher’s liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection system is capable of performing qualitative or quantitative analysis of inorganic or organic compounds derived from human blood samples. Analytes include endogenous substances such as amino acids, vitamins, and hormones, as well as therapeutic monitoring compounds, such as therapeutic/toxic drugs.

Furthermore, its triple quadrupole mass spectrometer can also be used for the qualitative or quantitative detection of inorganic or organic compounds in human biological samples, such as whole blood, plasma, serum, urine, cerebrospinal fluid, saliva, and tissue homogenates.

Shimadzu’s high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system enables qualitative or quantitative analysis of analytes in human blood samples, such as amino acids, carnitine, and vitamins.

It should be noted that, although the clinical mass spectrometry industry is still characterized by the market dominance of foreign giants, a number of competitive clinical mass spectrometry products have emerged in the market, and the localization rate in the LC-MS field is steadily increasing.

For example, Yingsheng Biology has established a domestic production line for liquid chromatography-mass spectrometry (LC-MS) systems and launched high-performance domestically produced triple quadrupole mass spectrometers and high-performance domestically produced miniaturized mass spectrometers. In addition, in May 2023, Hexin Instruments released the LC-QTOF 7000, the first domestically developed quadrupole time-of-flight liquid chromatography-mass spectrometer independently researched and manufactured in China. This product integrates multiple core technologies, including a highly compatible LC-MS interface, a collision cell with low dwell time, a high-performance time-of-flight mass analyzer, a fast-response ion detector, and a newly patented ion flow valve, achieving numerous innovations in mass spectrometry.

However, regrettably, from 2023 to the present, despite numerous innovations in the research, development, and manufacturing of domestically produced mass spectrometers, with many companies having launched or preparing to launch Chinese-made mass spectrometers, we have not yet identified any typical achievements of domestically produced mass spectrometers in clinical applications at the commercialization level.

Meanwhile, the clinical application of LC-MS faces numerous challenges. First, current hospital-based LC-MS tests are concentrated in areas such as vitamin testing, therapeutic drug monitoring of psychotropic medications, steroid hormone analysis, and newborn screening, which limits their economic viability. Second, the large-scale implementation of mass spectrometry in clinical settings is hindered by high costs and difficulties in achieving standardization and automation. These are critical issues that enterprises and regulatory authorities must address in the future.