New laser tweezers allow gentle, efficient manipulation of cells and nanoparticles (w/video)
(Nanowerk Spotlight) Optical tweezers have been a cornerstone technology for manipulating microscopic objects in various fields, including biotechnology and materials science. However, they have limitations, such as the need for high laser power and specific environmental conditions, which can cause thermal and photon damage to sensitive biological samples.
Traditional optical tweezers operate by trapping target objects with a laser, the effectiveness of which depends on factors like the refractive index of the object and the surrounding medium. High laser power is often required, especially when the object has a low refractive index contrast with its environment. This can be problematic for biological samples, as the high power can induce thermal damage and reduce cell viability. Various adaptations of optical tweezers have been developed to address these issues, but they often require complex setups or are limited in their applicability.
Researchers at the University of Texas at Austin have developed a new laser-based technique called hypothermal opto-thermophoretic tweezers (HOTTs), which rely on thermophoresis - the motion of particles along a temperature gradient - that allows for precise manipulation of cells, nanoparticles, and other micro-objects using extraordinarily low laser power.
Working principle of HOTTs. (a) At ambient temperature, thermophoretic force (Fth) repels the particle away from the laser in most conditions. White arrows indicate Fth decomposed along and perpendicular to the substrate (b) In HOTTs, Fth becomes attractive to trap particles at a sub-ambient temperature. c Schematic and timelapse optical images showing the repelling of a 1 µm PS particle inDI water by the laser beam at an ambient temperature of 27 °C. d The same particle was trapped at the laser beam at a sub-ambient temperature of 4 °C. The green crosshair indicates the laser beam center. Laser wavelength: 532 nm, laser power: 40 µW, beam radius: 850 nm, scale bars: 2 µm. (≅ Nature Communications) (click on image to enlarge)
“HOTTs offer a more versatile and gentle approach by combining localized laser heating with environmental cooling,” first author Dr. Pavana Siddhartha Kollipara, a graduate research assistant in the Zheng Research Group at UT Austin, tells Nanowerk. “This dual-action method allows for the low-power trapping of a wide range of particles and biological cells while minimizing the risk of thermal damage. The cooling strategy also enhances the thermophoretic trapping force, making it possible to trap particles in a wider range of conditions.
The working principle of HOTTs involves a thermoplasmonic substrate that generates a temperature gradient under local laser heating. By heating nanoparticles and cells with a focused laser, researchers can generate temperature gradients in the surrounding liquid that pull the objects toward the hotter region near the laser focus. Since it doesn't rely on scattering and refractive forces, opto-thermophoretic trapping requires 2-3 orders of magnitude less laser power than optical tweezers.
However, opto-thermophoretic tweezers have their own drawbacks. The laser heating needed to generate thermophoretic forces can still cause thermal damage. And for biological cells, which tend to move away from heat, tweezing requires adding surfactants or salts to make the cells thermophilic.
HOTTs take opto-thermophoretic trapping to the next level by adding cooling. "We couple environmental cooling with localized laser heating to achieve low power thermophoretic trapping of target objects and simultaneously avoid optical and thermal damage," explains Kollipara.
The researchers built a temperature-controlled sample stage with a Peltier cooler that cools the liquid sample down to 4 °C. The lower temperature makes otherwise thermophobic particles and cells thermophilic, so they move toward the laser hotspot. Cooling enhances this thermophoretic force 10-fold while also suppressing laser heating damage.
"The enhanced thermophilic nature of the particles increases the trapping force magnitude," says Kollipara. "And the hypothermal temperature further facilitates the noninvasive trapping of fragile objects like cells."
Kollipara and colleagues demonstrated HOTTs by manipulating a variety of synthetic microparticles, showing the tweezers can stably trap beads of different materials, sizes, and concentrations.
One of the most compelling applications of HOTTs is in the field of biotechnology, specifically for trapping biological cells like erythrocytes (red blood cells). Traditional methods have been limited to trapping these cells in isotonic solutions and often result in thermal damage. HOTTs, however, were able to trap erythrocytes in different tonicities—hypertonic, isotonic, and hypotonic—without causing thermal rupture, opening new avenues for disease diagnostics and cellular studies. This capability could enable new studies of red blood cell mechanics and interactions to uncover insights about diseases like sickle cell anemia and malaria.
Finally, the researchers used HOTTs to grab and manipulate nanoscale drug-delivery vehicles called plasmonic vesicles. With two laser beams, they positioned vesicles in 3D then triggered them to release their drug payload on demand.
"With their versatility and general applicability, HOTTs will have many potential applications in disease diagnostics, thermal therapy, drug delivery, and microrobotic surgery," said senior author Yuebing Zheng, an engineering professor at UT Austin.
The researchers say that because HOTTs rely on intrinsic particle properties, they can manipulate and study a wide range of synthetic and biological micro-objects without chemical additives or substrate modifications.
"We can extend this technique to trap different soft matter systems like polymers, proteins etc. by tuning the environmental conditions," Kollipara concludes. "HOTTs can additionally be extended to non-plasmonic targets by using a plasmonic or light-absorbing particle as a delivery agent."
The significance of this work lies not just in its immediate applications but also in its potential to spur further innovations in materials science and biotechnology. By offering a non-invasive, versatile, and efficient method for trapping microscopic particles and biological cells, HOTTs could become an invaluable tool for researchers and professionals in various scientific disciplines.