Bio-sensors (Note 1) are biomolecular sensors that leverage or mimic the sophisticated molecular recognition capabilities of living organisms. They find widespread applications in fields such as healthcare, food, and the environment. In particular, optical biosensors, which optically read the interactions between target molecules and molecular recognition elements, offer high precision and rapid measurement capabilities. However, they have proven insufficient in terms of sensitivity for the ultra-early detection of novel coronavirus (SARS-CoV-2) and cancer cells.
The research group comprising Prof. Takeshi Yasui and Visiting Associate Professor Taira Kajisa of Institute of Post-LED Photonics, Tokushima University; Doctoral Course Student Shogo Miyamura of the Graduate School of Advanced Technology and Science, Tokushima University; and Associate Prof. Shuji Taue of the School of System Engineering, Kochi University of Technology has applied optical frequency comb (OFC) (Note 2), which have been gaining attention as the next-generation lasers, not as light sources but as sensors for biosensing(Note 3). In this research, we utilized the unique optical-to-electrical frequency conversion properties of OFC in order to address the aforementioned challenges, enabling sensing in the optical frequency domain and reading out in the electrical frequency domain. Furthermore, by employing twin OFCs (dual OFC) and implementing active-dummy temperature compensation(Note 4), we successfully mitigated the common issue of temperature drift(Note 5) in biosensing.
This breakthrough has enabled rapid and highly sensitive detection of SARS-CoV-2 and holds promise for ultras-early detection of emerging and re-emerging infectious viruses, as well as health biomarkers including cancer and environmental contaminants that pose health risks.
Terminology
(Note 1) Biosensor
A biosensor is a device or sensor that detects biological or biochemical processes and converts them into electrical signals, optical signals, or other forms of signals. Typically, it involves immobilizing bio-derived molecules (such as enzymes or antibodies) on the sensor surface and detecting changes when target molecules bind to them. Biosensors are known for their high sensitivity and rapid measurement capabilities, making them valuable tools for applications ranging from monitoring blood glucose levels and detecting proteins to assessing environmental and food safety, identifying harmful substances and bacteria, and
more recently, detecting novel coronavirus. They find applications in health and disease management, environmental monitoring, public health, and various fields.
(Note 2) Optical frequency comb (OFC)
OFC is a discrete multi-spectral structure comprising narrow-linewidth laser light (optical frequency modes) that can range from tens of thousands to several hundred thousand modes, uniformly spaced like the teeth of a comb. Through frequency stabilization control, it is possible to precisely determine the absolute frequencies of all the optical frequency modes that constitute the OFC. Consequently, OFC has been employed as "optical frequency rulers" in applications like gas spectroscopy analysis. In this context, our novel approach utilizes the OFC as an "optical-to-electrical frequency converter." This opens up new avenues for applying OFC in the field of biosensing.
(Note 3) Biosensing
Biosensing refers to a set of techniques, methods, or approaches used to detect, monitor, or measure biological or biochemical processes using biosensors. Biosensing encompasses the entire process of utilizing biosensors to collect and interpret data.
(Note 4) Active-dummy temperature compensation
Active-dummy temperature compensation is a commonly used technique for compensating temperature effects in strain gauges (strain sensors). Strain gauges are sensitive to both strain and temperature, making it challenging to accurately measure strain in environments with temperature variations. To address this issue, an equivalent pair of strain gauges is prepared. One strain gauge is attached to the site where strain is measured (active strain gauge), while the other is placed nearby in a location where strain does not occur, but temperature changes are expected to be similar (dummy strain gauge). While the active strain gauge measures both strain and temperature changes, the dummy strain gauge only measures temperature changes. By calculating the difference signal between the two gauges using a bridge circuit, the influence of temperature changes is effectively canceled out, allowing for the measurement of strain alone.
(Note 5) Temperature drift
In biosensing, temperature drift refers to the phenomenon where changes in temperature, either in the biosensor itself or in the biological sample, can influence the measurement
results of the biosensor. Temperature drift is an important factor that needs to be taken into consideration when biosensors are used to perform accurate measurements.