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Optical Device Rapidly Detects Biomarkers in Urine

By LabMedica International staff writers
Posted on 22 Mar 2016
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Image: Schematic diagram of the MZI biosensor system for miRNA detection. (a)TEM image of the cross section of a silicon nitride slot wave guide; SEM images of (b) a strip-slot wave guide mode converter and (c) a silicon nitride grating coupler. (d) Image of MZI biosensor platform (Photo courtesy of Agency for Science, Technology and Research).
Image: Schematic diagram of the MZI biosensor system for miRNA detection. (a)TEM image of the cross section of a silicon nitride slot wave guide; SEM images of (b) a strip-slot wave guide mode converter and (c) a silicon nitride grating coupler. (d) Image of MZI biosensor platform (Photo courtesy of Agency for Science, Technology and Research).
A compact optical device has been developed that can rapidly and sensitively detect biomarkers in urine and has promise for developing simple point-of-care diagnostics of cancer and other diseases.

Micro ribonucleic acids (miRNAs) are a newly discovered class of short, about 19 to 24 nucleotides in length, fragments of noncoding RNAs that are useful biomarkers for diagnosing various diseases, including cardiac disease and some cancers. Since they are surprisingly well preserved in fluids such as urine and blood, their detection is well suited to a rapid, point-of-care method.

Bioengineers at the Agency for Science, Technology and Research (Singapore) have devised a silicon photonic biosensor that can detect tiny changes in the phase of a light beam caused by hybridization between an immobilized DNA probe and target miRNAs in a sample. A laser beam travels through a waveguide, which splits into two arms: a sensing arm in which the light interacts with the sample and a reference arm. The two light beams then rejoin each other. Binding between the DNA probe and the target miRNA alters the phase of the light traveling in the sensing arm, whereas the phase in the reference arm remains unchanged. The amount of target miRNA in the sample can be determined by monitoring the variation in the intensity of the output beam.

To demonstrate the system, the team used it to detect two types of miRNAs in urine samples from three patients with late-stage bladder cancer; the tests involved a single reaction and took 15 minutes. The microRNA levels of the patients differed markedly from those of two healthy subjects. Mach–Zehnder interferometer (MZI) biosensor was fabricated using standard complementary metal-oxide-semiconductor (CMOS) processes. For the optical characterization of the MZI sensor, the light coming from a TSL-510 tunable laser (Santec; Komaki, Japan) at a wavelength 1,562 nm passes through a polarization controller and a fiber pigtailed collimator.

Mi Kyoung Park, PhD, the principal investigator, said, “Existing methods to detect microRNAs are time consuming and require cumbersome machines, which limit their usefulness in clinical settings. This inspired us to develop a simple and efficient point-of-care device for detecting microRNAs. The device is also highly sensitive and thus does not require labeling or amplification; it can deliver results within 15 minutes, eliminating the need for patients to return for their results; and it can potentially detect up to 16 targets in a single test.” The study was originally published in the September 2015 issue of the journal Biosensors and Bioelectronics.

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