HUN-REN Biological Research Centre, Szeged Institute of Biophysics, Temesvári krt. 62, Szeged, 6726, Hungary.
Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, 6720, Hungary.
Adv Mater. 2024 Aug;36(32):e2401115. doi: 10.1002/adma.202401115. Epub 2024 Jun 5.
Precisely controlled manipulation of nonadherent single cells is often a pre-requisite for their detailed investigation. Optical trapping provides a versatile means for positioning cells with submicrometer 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 tens of pN range and present three modes of single-cell manipulation as examples to showcase the possible applications such soft microrobotic tools can offer are characterized. The applications describe here include cell collection, 3D cell imaging, and spatially and temporally controlled cell-cell interaction.
精确控制非黏附性单细胞的操作通常是对其进行详细研究的前提条件。光学捕获提供了一种通用的方法,可以以亚微米精度定位细胞,或以飞牛分辨率测量力。该技术的一种变体,称为间接光学捕获,通过依赖于与细胞结合的生物化学结合的光学捕获微工具,实现了无光损伤、优越的空间控制和稳定性的单细胞操作。高分辨率 3D 光刻技术可用于制备具有任何预定义形状的此类细胞操作器,从而大大扩展了可实现的操作任务数量。这里首次提出了一种新型的细胞操作器家族,它们可以通过光镊变形,并依靠其弹性来固定细胞。这通过避免用于细胞附着的生化功能化提供了一种更直接的间接光学捕获方法,并且可以随时释放被操作的细胞。使用光致抗蚀剂 Ormocomp,在数十皮牛顿范围内的光力作用下可实现的变形,并以三种单细胞操作模式为例,展示了这种软微型机器人工具可以提供的可能应用。这里描述的应用包括细胞收集、3D 细胞成像以及空间和时间控制的细胞-细胞相互作用。