Optimized Optical Tweezers Look Before Grabbing

Optical tweezers working in tandem will one day be able to grasp and manipulate cell clusters with a high level of dexterity, according to research from the University of Freiburg. The work would allow greater study of tiny objects such as miniature tumors.

Computer-holographic optical tweezers capable of multiplied configurations are already used to control the positions of several optical tweezers simultaneously in 3D space. However, the method is unable to exert control over objects larger than approximately 1/10 mm; the tweezers run into difficulties because the size of the objects make finding an optimal grabbing position difficult, causing the tweezers to lose their grip.

The reason the tweezers can’t find a good position is because they aren’t looking for it. Rather, they rely on the scientist using the tweezers to position them.

(a) Cell cluster without coverslip, in a rotating gel cylinder and contact-less in multiple optical tweezers. (b) Time-lapse from a 70-µm large cell cluster rotated around the x-axis (parallel to the image plane) by three dynamic, but blind, optical traps. The xy position of the rotation center is marked by a red cross, and the changing centers of the optical traps are marked by green crosses (with marker sizes proportional to the axial position). Courtesy of Nature Communications.

“Non-blind tweezers see what they are grabbing at by measuring and analyzing the light scattered on the object,” said Alexander Rohrbach, a professor in the Department of Microsystems Engineering. “We see various objects with our eyes because sunlight or indoor light is scattered on them and reproduced on our retina.”

One of the advantages of optical tweezers is their ability to grab through transparent objects. However, the biological research objects studied under the microscope — for example, cell clusters such as miniature tumors or small fly embryos — are not completely transparent. They behave more like frosted glass in a bathroom window, where the light is diffuse after transmission and therefore difficult to analyze.

To overcome this, the researchers analyzed the defocused laser-scattered light on a fast camera behind the object, which served as a feedback signal. The more asymmetrical the spots of light from the individual optical tweezers are on the camera, the more the light at the focus is scattered, leading to a greater change in the refractive index at the respective point in the object. These are the points at which the optical tweezers can efficiently grab at the object.

According to Rohrbach, the surprising thing about the principle of localizing the best grabbing position is that the light scattering — or the change in momentum — is much stronger directly in the laser focus than in front of or behind the focus. Each of the approximately five to 10 optical tweezers should feel the best grabbing position on the basis of the scattered light in order to rotate the object in different directions. If one of the tweezers exerts too much force, though, the other tweezers can lose their hold.

Rohrbach envisions that in the case of success, the principle of contactless sample holding will be integrated into the microscopes of the future.

The research was published in Nature Communications (www.doi.org/10.1038/s41467-021-27262-z).