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New Semiconductor Microchip Detects Prostate Cancer Markers with Ultra-High Sensitivity

This minimally invasive technique is expected to enable the widespread application of IoT biosensors, simplifying tests and remote medical examinations.

Researchers of the Department of Electrical and Electronic Information Engineering at Toyohashi University of Technology have developed a semiconductor sensor that can detect ultra-low concentrations of tumour markers on chips. Produced using semiconductor micromachine technology, these testing chips, sized as small as several millimetres across, are expected to be applied in IoT biosensors for home-based testing.

Measuring devices that can simply and rapidly perform disease tests using small amounts of blood, urine, saliva, or other bodily fluids have long been recognised as valuable tools for accurate diagnosis and verifying the effectiveness of therapeutic treatments. These devices generally measure biomarkers, or substances that change in concentration according to the specific diseases in bodily fluids, to provide insight into the presence or progression of the disease. During the COVID-19 pandemic, which necessitated rapid diagnosis of the disease at unprecedented scales, measuring devices allowed clinicians to monitor specific biomarkers in patients, which helped predict the severity of disease.

In cancer, screening methods for early detection also play a vital role. For instance, the prostate-specific antigen (PSA) test is widely used to screen for prostate cancer. To test for PSA, marker screening of saliva may be performed as a less invasive alternative of cancer risk testing. The commonly used PSA marker testing equipment operates by detecting colour changes using a labelling agent. However, due to the laborious and time-consuming process of labelling and the relatively large size of these equipment, the use of this method is limited to large hospitals.

In their recent study, Associate Professor Kazuhiro Takahashi, Tomoya Maeda, and colleagues have found a way around these problems by developing a novel micro-scale testing chip that can detect the presence of prostate cancer antigen by adsorbing disease-derived marker molecules present in blood and other bodily fluids into the surface of a flexibly deforming nanosheet. To actualise this, the team leveraged the principle of converting the force caused by the interaction between the adsorbed molecules into the amount of deformation of the nanosheet.

Their approach works by fixing antibodies, which serve to catch marker molecules (antigens), onto the nanosheet in advance. The film would then deform as a result of the force of the adsorbed antigens electrically repelling each other, from which the deformation can be read. Because this sensor was designed to deform sensitively in response to the adsorption of biomolecules, the film may deteriorate as a result of fixing antibodies onto it. Previous methods of producing the biological functional layer on the surface, which involves ultraviolet irradiation, could also degrade the nanosheet films. Therefore, the research team adopted an alternative method of depositing the functional layer via chemical vapour deposition. Their resultant sensor chip was thinner, more uniform, and less degraded.

To test their device, Takahashi, Maeda, and team performed an experiment to detect prostate cancer biomarkers. It was found that their device could detect 100 attograms, equivalent to three attomolars in terms of molar concentration, contained in one millilitre of fluid. Since this lower limit detection concentration is comparable to that of large testing devices using labelling agents, their technology is hoped to be applied in ultra-sensitive testing with portable-scale testing devices. In addition, because the scientists can detect how nanosheets deform by adsorption of molecules in real-time, their device may be able to detect disease-derived molecules faster than standard testing equipment that use labelling agents.

With these optimistic results, the scientists are now planning to demonstrate the practical application of their innovation in portable testing equipment by showing how biomarkers can be detected on semiconductor sensors that integrate analytical integrated circuitry. By simply replacing probe molecules to the surface of nanosheets, numerous types of comprehensive disease diagnosis tests can be developed, potentially allowing early-stage detection of more diseases in the future. [APBN]

Source: Maeda et al. (2022). Bio-Interface on Freestanding Nanosheet of Microelectromechanical System Optical Interferometric Immunosensor for Label-Free Attomolar Prostate Cancer Marker Detection. Sensors, 22(4), 1356