Detecting Pathogens with Swimming Gold Nanoparticles

Toshiharu Saiki (Professor, Department of Electronics and Electrical Engineering)

"Isn't there a way to make flu tests less painful?" "Can't cancer be detected earlier?" Everyone hopes for highly accurate medical diagnostics that are less burdensome for patients. To meet these demands, the challenge, simply put, is to unerringly detect the viruses, bacteria, or disease-signaling substances that cause illness, no matter how small the quantity. This is a universal theme for researchers in biosensing, with new methods being proposed and demonstrated daily. In our laboratory, we are also working on developing highly sensitive sensing methods based on our accumulated nanophotonics technology. Here is one example.

One key to high sensitivity is making the object of interest (hereafter referred to as the "target") "easy to find." For this purpose, we chose a method of capturing the target with brightly shining gold nanoparticles. This is a common and widely used technique. Using antigen-antibody reactions or the binding of complementary DNA strands, we capture the target antigen or DNA by sandwiching it between two gold nanoparticles (this is called forming a dimer; see Figs. 1 and 2).

Fig. 1: Antibodies that bind strongly to the target antigen (virus) are attached to gold nanoparticles in advance. When the gold nanoparticles and antigens meet in water, pairs of gold nanoparticles (dimers) are formed with the antigen acting as an adhesive. Dimers are formed in a similar way when the target is DNA.

Fig. 2: An isolated gold nanoparticle (left) and its dimer (right) observed with an electron microscope. The two particles are joined by DNA binding. The diameter of the gold nanoparticles is 40 nm.

In other words, when a specimen is added to an aqueous solution of gold nanoparticles used as a reagent, dimers appear in proportion to the amount of the target. Furthermore, "fast detection" is crucial in clinical settings, so methods that require minimal separation and washing steps are desirable. Therefore, we decided to directly identify whether each gold nanoparticle undergoing Brownian motion in water is an isolated particle (which has not captured a target) or a dimer (which has captured a target) by checking them one by one. By focusing on the differences in optical anisotropy and rotational speed, we can instantly and unerringly distinguish between the two (Fig. 3). Also, since this method digitally counts the number of particles, it is a robust method unaffected by noise or changes in the surrounding environment, making it suitable for on-site use.

Fig. 3: Under a microscope, a laser beam is focused to a small spot to observe the swimming gold nanoparticles one by one. Compared to isolated particles, dimers have the property of changing the polarization of scattered light and also exhibit slower rotational motion. By observing the particles with these two points in mind, isolated particles and dimers can be instantly distinguished.

Having completed the basic proof-of-principle, we are now working on expanding the types of targets and developing a device. You might wonder, "Do they do this kind of bio-related research in the Department of Electronics and Electrical Engineering?" However, because students in the Department of Electronics and Electrical Engineering have a solid foundation in areas such as optoelectronic measurement, signal processing and communication, and device technology, they can smoothly create new practical technologies with a view of the entire system when collaborating with people from different fields.