Researchers often use antibodies to detect specific molecules or biological markers, as they are remarkably precise at recognizing their targets. However, finding the faint signals of cancer in blood samples is a challenge even for the most reliable techniques.
Osaka Metropolitan University researchers have now found that these molecular detectors can get a little boost by adding some extra light. Using laser irradiation, they accelerated antibody–antigen interactions, detecting tiny amounts of a colorectal cancer biomarker within minutes.
Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Early detection remains an important line of defense, one that scientists are working to strengthen.
"Current blood-based tests for cancer biomarkers often require lengthy preparation steps and have limited sensitivity when biomarker levels are extremely low," said Takuya Iida, professor at the Graduate School of Science and Research Institute for LAC-SYS (RILACS) at Osaka Metropolitan University and lead author of this study.
"We aimed to develop a faster and more sensitive method for detecting glycoprotein CEACAM-5, a biomarker associated with colorectal cancer."
Conventional methods for measuring disease biomarkers often use immunoassays, in which antibodies recognize and bind to specific target proteins. The binding event is then converted into a detectable signal, often through an enzyme attached to an antibody.
However, such assays can require hours of incubation and washing steps, besides which detecting a target protein in blood can be a real challenge as it is surrounded by thousands of other proteins and many other substances.
The researchers attached multiple antibodies to microscopic beads and introduced them into a tiny flow channel containing blood plasma. When a laser was applied, the Light-induced Acceleration System (LAC-SYS) enhanced interactions between the antibody-coated beads and CEACAM-5, causing the beads to assemble. The researchers could then measure the resulting bead assemblies as a signal for the presence of CEACAM-5.
"Our light-induced detection technology can detect extremely small amounts of CEACAM-5 in blood within just a few minutes compared to several hours for conventional techniques," Iida said.
Their method detected CEACAM-5 at concentrations of 1–10 picograms per milliliter in diluted blood plasma about the size of a sesame seed. 5 µL of plasma was serially diluted for each experiment, and 1000-fold diluted samples were mainly used from patients with colorectal cancer. This represents a potential improvement of one to two orders of magnitude over the detection range of conventional immunoassays, such as enzyme-linked immunosorbent assays and immunoprecipitation. The researchers also uncovered something unexpected about the cancer biomarker itself.
"We found that CEACAM-5 exists in blood as nanoscale aggregates," Iida said.
These clusters may interact efficiently with the antibody-coated beads, helping them assemble and producing a stronger detectable signal. This might explain how the system detects CEACAM-5 at such low concentrations.
The findings could have implications beyond colorectal cancer. Since the technology relies on antibody recognition, the researchers hope to adapt it to other disease-related biomarkers, including those associated with dementia and infectious diseases.
"Our findings may facilitate earlier and less invasive cancer detection and open new possibilities for liquid biopsy technologies," Iida said.
The next step is to validate the technology in clinical settings and determine how reliably it can distinguish disease-related signals. The team also aims to work with industry partners to develop practical, portable diagnostic systems.
"Ultimately, our goal is to establish a rapid, highly sensitive, and minimally invasive platform for liquid biopsy and other blood-based diagnostic technologies that can support earlier disease detection and intervention," Iida said.
The study was published in Nanoscale Horizons.
