Precisely controlled manipulation of non-adherent single cells is often a prerequisite for their detailed investigation. Optical trapping (OT) provides a versatile means for positioning cells with sub-micrometer precision or measuring forces with femto-Newton resolution. A variant of the technique, called indirect optical trapping, enables single-cell manipulation with no photodamage and superior spatial control and stability by relying on optically trapped microtools biochemically bound to the cell. High-resolution 3D lithography enables to prepare such cell manipulators with any predefined shape, greatly extending the number of achievable manipulation tasks.
Here, it is presented for the first time a novel family of cell manipulators that are deformable by optical tweezers and rely on their elasticity to hold cells. This provides a more straightforward approach to indirect optical trapping by avoiding biochemical functionalization for cell attachment, and consequently by enabling the manipulated cells to be released at any time. Using the photoresist Ormocomp, the deformations achievable with optical forces in the 10s of pico-Newton range and present 3 modes of single-cell manipulation as examples to showcase the possible applications such soft microrobotic tools can offer are characterized.
The applications described here include cell collection, 3D cell imaging, and spatially and temporally controlled cell-cell interaction.
Figure 4: Cell tweezers structure and its application for multiview microscopic imaging.
(A) Schematic view of the non-adherent cell held with the cell tweezers structure.
(B) Electron micrograph of the cell tweezer structure; the flexible rods are highlighted with red, the cell holding pins with green.
(C) Brightfield microscopy snapshots of the cell collection procedure.
The yellow stars mark the position of the OTs.
(D) Fluctuation of a cell measured in a stationary position held with an optically trapped tweezers structure.
(E) Brightfield-fluorescence composite images of a fluorescent nanobead-labeled cell held with the tweezers structure in two different orientations reached by rotating the microstructure by 90° with the OT.
(F) Maximum intensity projection images of aligned image stacks recorded on fluorescent bead-decorated cells originating from 4 different orientations and that of the fused image stack.
(G) Normalized intensity traces observed along the z and x-axes on the bead marked with a yellow arrow on panel (F). The more than 3× reduction of the image width along the z-axis demonstrates the resolution enhancement.