Development of semiconductor microchip that can detect prostate cancer markers with ultra-high sensitivity

Source: Toyohashi University of Technology, by ecancer (March 7, 2022). AI-generated summary by biochip.com, published April 11, 2026. Not independently reviewed.

Researchers at Toyohashi University of Technology have built a semiconductor sensor chip that detected an extremely small amount of a prostate cancer biomarker: 100 attograms in one milliliter of fluid, equivalent to three attomolar in molar concentration. The device uses a thin, flexible nanosheet that bends when target molecules bind to antibodies attached to its surface. Rather than relying on a color-changing label, the sensor reads physical deformation caused by interactions among the captured molecules. That label-free approach could make testing simpler and faster while shrinking it toward a portable format. The millimeter-scale chips were made with semiconductor micromachining methods, the same broad family of manufacturing techniques used to create very small electronic structures. The team focused on prostate-specific antigen, or PSA, a blood marker that can rise with prostate cancer. Its reported detection limit matched that of larger testing systems that use labeling agents. The researchers now aim to combine the sensor with analytical integrated circuitry as a step toward portable, connected biosensors for testing bodily fluids.

A tiny sheet that responds to captured molecules

The Toyohashi University of Technology team, including Associate Professor Kazuhiro Takahashi and master's student Tomoya Maeda, designed the device around a nanosheet, an exceptionally thin film that can flex in response to minute forces. Think of it like a trampoline stretched tightly enough that even a few added objects subtly change its shape. In this case, the objects are biomarker molecules captured from a liquid sample.

Before testing, the researchers attach antibodies to the nanosheet. Antibodies are proteins that recognize and bind to particular molecular targets, much as a lock is designed for a specific key. When PSA molecules bind to those antibodies, the adsorbed molecules electrically repel one another, creating a force that deforms the thin film.

The sensor converts that deformation into a measurable signal. This mechanical strategy differs from many established laboratory tests, which use labeling agents to make a target molecule visible through a color change. By measuring the nanosheet's response directly, the chip can detect the presence of a disease-related molecule without waiting for a labeling step.

Why fabrication details mattered

The team faced a practical obstacle: attaching antibodies could damage the sensitive nanosheet. Earlier versions used spin coating and ultraviolet irradiation to form the biological functional layer, the surface layer that holds the antibodies. Ultraviolet exposure was considered one factor behind deterioration of the nanosheet film.

To address that problem, the researchers changed the materials and used chemical vapor deposition to deposit the functional layer. Chemical vapor deposition is a manufacturing process in which gaseous chemicals form a thin coating on a surface. The method produced a thinner, more uniform sensor structure with less damage to the underlying film.

That change matters because a sensor built to respond to tiny mechanical forces needs its flexible element to remain intact and consistent. A rough or degraded film could produce uneven responses, masking the minute deformation caused by a small number of captured molecules. The revised fabrication approach therefore supported both the chip's sensitivity and its potential reproducibility.

Detecting PSA at an attogram scale

Using the new biosensors, the team tested for prostate cancer biomarkers and reported detection of 100 attograms in one milliliter of fluid. An attogram is one quintillionth of a gram, written as 10 to the power of negative 18 grams. The reported mass corresponds to a concentration of three attomolar, a unit describing an exceptionally dilute molecular concentration.

The result is notable because the team said this lower detection limit was comparable to larger test instruments that use labeling agents. Conventional labeled assays can require multiple preparation steps and equipment that is more practical in major hospitals or centralized testing laboratories. The nanosheet device aims to deliver similar analytical sensitivity in a chip only several millimeters across.

PSA is among the most widely used cancer-associated marker tests. It can increase in the blood as a result of prostate cancer, though a biomarker signal is not itself a diagnosis. The work demonstrates that the semiconductor chip can recognize PSA molecules selectively through the antibodies placed on the nanosheet surface.

From laboratory assays to connected testing

The group sees the platform as a possible Internet of Things, or IoT, biosensor. IoT devices connect or exchange data electronically, which could allow a testing device to share measurements with remote clinical systems. The researchers envision home-based testing using small amounts of blood, urine, saliva, or other bodily fluids.

Portability could matter because disease monitoring often depends on making tests accessible and repeatable. A compact device that reduces preparation steps may expand where measurements can be performed, including settings outside large hospitals. The team also noted that reading nanosheet deformation in real time could detect disease-derived molecules faster than systems that depend on labeling agents.

The same physical chip concept may be adapted for different targets by replacing the probe molecules placed on the nanosheet. Here, the probes were antibodies designed to catch prostate cancer antigens. In principle, different surface probes could allow related chips to look for other disease-associated molecules.

Why This Matters

This work puts a sensing element, rather than just supporting electronics, at the center of a semiconductor chip. Its nanosheet translates molecular binding into a mechanical change, linking biological recognition directly to a physical signal that can be measured electronically. That combination is central to the promise of lab-on-a-chip diagnostics: moving a complex laboratory measurement into a small, engineered device.

The reported PSA result also shows why manufacturing methods can shape biological performance. The sensor did not become more useful simply because it was smaller. Its performance depended on preserving a delicate deformable film while building an antibody-bearing surface that could selectively capture the intended biomarker.

Next, the Toyohashi team plans to demonstrate biomarker detection on semiconductor sensors that integrate analytical circuitry. If that integration works as intended, the platform could bring molecular capture, signal readout, and data handling closer together in a portable test device. Replacing the nanosheet's probe molecules could then extend the approach toward broader disease-screening applications and remote physician-supported testing.

Topics: Biosensors · Cancer · Diagnostics & precision medicine

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