A Japanese research team has developed an efficient and minimally invasive cancer detection device that uses high-performance zinc oxide nanowires to selectively capture extracellular vesicles (EVs) from body fluids.
The researchers used this device to successfully capture cancer-associated EVs from the serum of ovarian cancer patients. The surface membrane proteins and microRNAs of EVs remained intact, demonstrating the potential for sensitive disease analysis. These findings were published in the journal device.
Liquid biopsy is a procedure that collects disease-related information from body fluids such as blood and urine. Unlike traditional tissue biopsy, it reduces the physical burden on the patient.
EVs are nanoscale vesicles that carry diverse molecular contents such as microRNAs and messenger RNAs and display membrane proteins that indicate their cell of origin. EV reflects the disease state and serves as a promising diagnostic indicator for liquid biopsy.
Accurate and efficient isolation of EVs from complex body fluids is essential for identifying disease-associated molecules, but traditional techniques are time-consuming, require large sample volumes, and lack specificity.
A team led by Takao Yasui, a professor at the Nagoya University Graduate School of Engineering, succeeded in efficiently capturing EVs using the developed zinc oxide nanowires.
They are currently collaborating with Professor Yasuhide Inokuma of Hokkaido University and researchers from Tokyo University of Science, Kyoto University, and the National Institute for Quantum and Radiological Science and Technology to develop antibody-conjugated nanowire technology to selectively capture cancer-derived EVs.
The first challenge was attaching antibodies to the nanowires. Traditional adhesives bind both target and nonspecific proteins and require long adhesion times.
The research team used synthetic polymer polyketones to create six N-hydroxysuccinimide-functionalized polyketone (pKNHS) variants with different chain lengths. Among these, pKNHS 4.2 showed optimal stability for adsorption onto zinc oxide nanowires and effective antibody immobilization, allowing single-step antibody modification.
Evaluation of new technology in cultured cell experiments
Researchers used pKNHS 4.2 to evaluate the capture efficiency of antibody-conjugated nanowires on cultured breast cancer cells. Antibody-free nanowires captured approximately 65% of CD9-positive EVs, whereas CD9 antibody-conjugated nanowires achieved 90% efficiency. These results demonstrate the effectiveness of the technique to selectively recover target molecules.
Further experiments showed that nanowires modified with antibodies against ovarian cancer markers CLDN3, FOLR1, and TROP2 enabled selective recovery of EVs from ovarian cancer cells.
Analysis of serum from cancer and non-cancer patients
Researchers used CLDN3, FOLR1, and TROP2 antibody-modified nanowires to isolate EVs from the serum of six patients with high-grade serous ovarian cancer, a highly aggressive subtype of ovarian cancer, and six non-cancer patients. Analysis of microRNAs in EVs revealed different profiles between patient and non-cancer groups.
The researchers compared microRNAs in EVs captured by the three antibodies and identified 126 microRNAs that were common to all, indicating a common signal in ovarian cancer. They also found microRNAs that were unique to each antibody. There were 40 for CLDN3, 37 for FOLR1, and 45 for TROP2. These findings suggest that EVs with different membrane proteins have different microRNA profiles.
Significance and future prospects
“In this study, we developed a nanowire microfluidic device that can selectively capture cancer-related endoplasmic reticulum with high efficiency while suppressing nonspecific adsorption through simple chemical modification,” said Yasui, corresponding author of the study.
We also demonstrated that this approach kept both EV membrane proteins and internal microRNAs intact, indicating strong potential for sensitive analysis of cancerous conditions. ”
Takao Yasui Nagoya University
“We plan to compare and evaluate this technology with existing clinical methods and expand its application to capture more specific EV subpopulations,” said Kunanon Chattrairat, assistant professor and corresponding author. “In the long term, we aim to apply this technology to non-invasive liquid biopsies and early diagnosis of various types of cancer.”
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Reference magazines:
Chatrailat, K. others. (2026) Discrete polyketones enable antibody click conjugation for selective exosome profiling. device. DOI: 10.1016/j.device.2026.101153. https://www.cell.com/device/fulltext/S2666-9986(26)00105-5?_returnURL=
