Automated Indirect Transportation of Biological Cells with Optical Tweezers and a 3D Printed Microtool

Abstract

Optical tweezers are widely used for noninvasive and precise micromanipulation of living cells to understand biological processes. By focusing laser beams on cells, direct cell manipulation with optical tweezers can achieve high precision and flexibility. However, direct exposure to the laser beam can lead to negative effects on the cells. These phenomena are also known as photobleaching and photodamage. In this study, we proposed a new indirect cell micromanipulation approach combined with a robot-aided holographic optical tweezer system and 3D nano-printed microtool. The microtool was designed with a V-shaped head and an optical handle part. The V-shaped head can push and trap different sizes of cells as the microtool moves forward by optical trapping of the handle part. In this way, cell exposure to the laser beam can be effectively reduced. The microtool was fabricated with a laser direct writing system by two-photon photopolymerization. A control strategy combined with an imaging processing algorithm was introduced for automated manipulation of the microtool and cells. Experiments were performed to verify the effectiveness of our approach. First, automated microtool transportation and rotation were demonstrated with high precision. Second, indirect optical transportations of cells, with and without an obstacle, were performed to demonstrate the effectiveness of the proposed approach. Third, experiments of fluorescent cell manipulation were performed to confirm that, indicated by the photobleaching effect, indirect manipulation with the microtool could induce less laser exposure compared with direct optical manipulation. The proposed method could be useful in complex biomedical applications where precise cell manipulation and less laser exposure are required.

Nanomanipulation in Biomedical Applications

“…However, the probe-based method is more favorable to realize a programable and an arbitrarily complex path. Even through cell-level robotassisted OT micromanipulation (automated cell transportation [104], PID control manipulation [105], high speed cell transportation [106], path planning in automated manipulation of biological cells [107] and so on) had made great achievements, it still lacks of a novel nanomanipulation exhibits a collection of advantages of two operating principles. Specifically, field-controlled nanomanipulation lacks the capability of generating an arbitrarily complex local distribution of the field.…”

4D Printing: Enabling Technology for Microrobotics Applications

“…The most developed stimulus is magnetic actuation which has been used to demonstrate planar and 3D positioning, multirobot actuation, and complex task excution (see Figure 1). [113][114][115][116][117][118][119][120] Some micromanipulation techniques not shown in Figure 1 are the following: optical trapping that can achieve 2D [121][122][123][124] and 3D [125,126] manipulation, as well as multiple objects manipulation. [127][128][129] Second, the generation and manipulation of microbubbles by means of temperature gradients induced by low power laser radiation was introduced by the study of Farahi et al [130] and then improved in the study by Ortega-Mendoza and co-workers.…”

Single-Cell Elasticity Measurement with an Optically Actuated Microrobot

“…Autonomous microrobots and microactuators have gained attention recently due to their ability to perform complex tasks on biological targets inside microfluidic environments (channels, reservoirs) without the administration of external physical tools. The targets of these manipulations include protein [ 1 ], DNA [ 2 ], their association [ 3 ] or single cells [ 4 , 5 ]. Furthermore, microtools have been developed to control the flow of the solvent that carries these biological objects [ 6 , 7 ] or to characterize their composition [ 8 ].…”

“…Since the size of these microrobots can range from sub-micrometers to a few hundreds of micrometers, they can be easily optimized for the manipulation of single cells. A broad range of tasks can be performed: cells can be actuated with the tools, which includes their simple translation or rotation either on a hard surface [ 4 , 5 ] or in 3D [ 11 , 18 ]; the tools can enhance imaging of cells [ 12 ]; the internal structure of the cells can be altered by punching holes in them with the tools [ 19 ]; and such microtools have a great potential even in performing cell-to-cell interaction experiments with high precision and selectivity.…”