Optical tweezers trap and manipulate minute particles with light. The technology is used across fields, ranging from manufacturing to biotech, though it requires the use of high-powered lasers to ensure proper function. These lasers can damage the trapped objects — especially if the objects are fragile, like living cells and nanoparticles. Making optical tweezers safer to use these fragile objects could broaden the use of this Nobel Prize-winning technology for applications such as cancer therapy and environmental monitoring. Researchers at the University of Texas at Austin (UT) developed a way to overcome the intense laser heating that causes optical tweezers to scorch biological objects. The approach, called hypothermal opto-thermophoretic tweezers (HOTTs), achieves low-power — and noninvasive — trapping of diverse biological cells and colloids in their native fluids. The tweezers combine environmental cooling and localized laser heating to realize low-power, thermophoretic trapping of target objects, while simultaneously avoiding optical and thermal damage. A new method makes optical tweezers safer to use for potential biological applications, such as cancer therapy. (a) Image shows schematic of red blood cells in solution. (b) Time-lapse showing trapping and thermal rupture at ambient temperature. (c) Time-lapse of trapping using new method. No cell rupture is observed. Courtesy of Nature Communications, doi: 10.1038/s41467-023-40865-y. “The main idea of this work is simple,” researcher Pavana Kollipara said. “If the sample is getting damaged because of the heat, just cool the entire thing down, and then heat it with the laser beam. “Eventually, when the target such as a biological cell gets trapped, the temperature is still close to the ambient temperature of 27 to 34 °C. You can trap it at lower laser power and control the temperature, thereby removing photon or thermal damage to the cells.” The researchers tested HOTTs on human red blood cells, which are sensitive to temperature changes. They demonstrated the trapping and manipulation of red blood cells in diverse tonicities, to mimic different bio-physio-chemical functionalities, and retained the structural integrity of the cell. According to Kollipara, performing this type of function using conventional optical tweezers damages the cell structure, and the cell dies immediately. HOTTs use a heat sink and Peltier cooler to keep the targeted particle cool. The researchers’ cooling strategy also facilitates thermophilic behavior that helps HOTTs trap diverse colloids at different conditions. The researchers showed that HOTTs can enable the consistent trapping of colloids at concentrations spanning several orders. The team further showed that HOTTs can be used to manipulate functional plasmonic vesicles — tiny biocontainers coated with gold nanoparticles — in 3D, for the purpose of light-controlled drug delivery. The researchers demonstrated the trapping and 3D manipulation of plasmonic vesicles by HOTTs, followed by controlled cargo release, using a dual laser beam setup. HOTTs can be extended to nonplasmonic targets by using a plasmonic or a light-absorbing particle as a delivery agent, the researchers added. “Laser-induced drug delivery is important because we can focus and deliver drugs on a particular target,” Kollipara said. “This way, the amount of drugs a patient consumes goes down significantly, and you can specify at what locations you can administer the drug.” HOTTs were developed and tested with the help of the Stampede2 supercomputer located at the Texas Advanced Computing Center at UT. Kollipara said that supercomputer simulations were necessary to compute full-scale, 3D force magnitudes on the particles from the optical, thermophoretic, and thermoelectric fields achieved at a specific laser power. The research was published in Nature Communications (www.doi.org/10.1038/s41467-023-40865-y).