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Nanowire Device for Microscopic Detection of Cancer Biomarkers in Urine

Analyzing microRNAs (miRNAs) within urine extracellular vesicles (EVs) is important for realizing miRNA-based, simple, and noninvasive early disease diagnoses and timely medical checkups. However, none of the existing methodologies for collecting EV-encapsulated miRNAs have satisfied the requirements for this- it is because the concentration of EVs in urine is extremely low.

Therefore, researchers at the Nagoya University have developed a novel medical device that can efficiently capture these EVs, and potentially use them to screen for cancer. “EVs are potentially useful as clinical markers.

Our developed device could allow us to collect thousands of urinary microRNAs from only 1 milliliter of urine,” said Takao Yasui, an assistant professor in the department of biomolecular engineering at Nagoya University and corresponding author on the paper.

The international team of scientists’ new approach relies on playing the forces of negatively charged EVs off of positively charged nanowires to extract the miRNAs from the urine of patients with a variety of diseases. In the case of the new Science study, they looked at samples from patients with pancreatic, liver, bladder, and prostate cancer, in addition to healthy subjects.

The researchers have developed  a microfluidic device comprising

zinc oxide nanowires embedded in a specialized polymer, which use electrostatic forces to collect miRNA-containing EVs from as little as 1 ml of urine. In initial tests, the device collected EVs encapsulating about 1,000 different types of miRNA sequence, far higher than the 200–300 different miRNAs that have been extracted from urine using conventional ultracentrifugation methods.

Surprisingly, the device could extract a much larger variety of species of miRNAs than ultracentrifugation despite the fact that the device uses a smaller sample volume and shorter treatment time than the latter method,” the authors state. The combined processes of nanowire capture of EVs and miRNA extraction also takes just 40 minutes.

Nanowire Device for Microscopic Detection of Cancer Biomarkers in Urine
Comparison of microRNA extraction using nanowires versus conventional collection. (a) Scatterplot comparing normalized intensities of microRNAs extracted with the nanowire device versus conventional collection by ultracentrifugation. (b) Histogram showing the frequency of microRNA species at different fluorescent intensities collected by nanowires (red) and ultracentrifugation (blue). Both the scatterplot and histogram analyses show a notably greater abundance of extracted microRNAs using the nanowire technology. Credit: Takao Yasui

Finding a specific, reproducible marker to help confirm a cancer diagnosis is difficult. This is especially true for microRNAs, which are a relatively new class of markers in the field,” co-author Yoshinobu Baba explains. “Sometimes finding just one reliable microRNA is considered a success. Using this approach, we were surprised to find that not just one, but whole combinations of microRNAs might be associated with different types of cancers. The findings are preliminary, of course, but we hope our device can help to lay the groundwork for easier ways to diagnose life-threatening diseases as early as possible.

Disha Padmanabha
In search of the perfect burger. Serial eater. In her spare time, practises her "Vader Voice". Passionate about dance. Real Weird.