Laser method puts white blood cells to work

Medicinal microrobots can help with drug delivery and other treatments via injection into blood cells. But this is highly invasive, and because both are made with synthetic materials, they often disrupt the normal physiological system in vivo.

“Once entering the body, microrobots tend to trigger the immune response,” says Xianchuang Zheng, a professor with the Institute of Nanophotonics at Jinan University (China). “They also face great challenges to cross the natural biological barriers—i.e., the vessel walls—so it’s hard to penetrate into the tissue to accomplish complex medical tasks.”

Now, Zheng and his team have discovered a different, more effective route.

Using scanning optical tweezers (SOTs), the team can precisely control natural neutrophils (white blood cells), with the intent of turning the cells into native medicinal microrobots. Unlike red blood cells that carry oxygen, the purpose of white blood cells is to fight infection. Such control includes remote activation, targeted navigation, and assisted transmigration (see Fig. 1).

In the study—published in ACS Central Science—SOTs were used to trap and manipulate neutrophils in zebrafish tails. Specifically, this involved pairing the SOTs’ laser (at a wavelength of 1064 nm) with an acousto-optic deflector, which spatially controls the beam, to achieve a spatiotemporal distribution (maximum switching rate) of 100 kHz. The laser beam was reflected by a dichroic mirror and focused through a 60× water immersion microscope. The focused laser beam was then irradiated on zebrafish to conduct multifunctional manipulation of neutrophils in vivo (see Fig. 2).

FIGURE 2. Rendering of the technique used by researchers to control a neutrophil microcraft.

“With the assistance of SOTs, a flowing neutrophil can be stably trapped in the blood vessel by the optical gradient force,” Zheng says. “After that, intelligent behavior control can be conducted for the neutrophil in a programmable manner. The basic actions of the neutrophil can be fully manipulated, such as directional movement, precise arrangement, controlled rotation, and dynamic deformation.”

Natural behavior maintained

The optical gradient force can essentially guide and promote the transmigration of the activated neutrophil across vessel walls. Throughout the process, the neutrophil maintains natural behavior, including phagocytosis (ingestion of bacteria with the aim of eliminating it). These behaviors can be actively and remotely controlled by SOTs on demand, allowing the native neutrophil to become a microcraft in vivo. And its migration can be precisely navigated to achieve a designed route and velocity.

“Most of the existing neutrophil-based strategies rely on the spontaneous chemotactic motion, lacking effective activation, rapid migration, and high navigation precision,” Zheng says. “As the first line of host defense against invading pathogens, neutrophils can serve as carriers for target loading via phagocytosis and to transmigrate across blood vessels to the infected tissue. This makes them natural candidates for the construction of medical microdevices in vivo.”

The team’s work could pave the way for development of biocompatible microrobots for biomedical applications such as targeted drug delivery and more precise disease treatments.

Citing the innate immunologic function of neutrophils and intelligent optical manipulation, Zheng says “this concept might provide new insight for the active execution of complex medical tasks in vivo, with great potential to treat inflammatory diseases.”