Intracellular manipulation and measurement with multipole magnetic tweezers

Abstract

The capability to directly interrogate intracellular structures inside a single cell for measurement and manipulation is important for understanding subcellular and suborganelle activities, diagnosing diseases, and developing new therapeutic approaches. Compared with measurements of single cells, physical measurement and manipulation of subcellular structures and organelles remain underexplored. To improve intracellular physical measurement and manipulation, we have developed a multipole magnetic tweezers system for micromanipulation involving submicrometer position control and piconewton force control of a submicrometer magnetic bead inside a single cell for measurement in different locations (spatial) and different time points (temporal). The bead was three-dimensionally positioned in the cell using a generalized predictive controller that addresses the control challenge caused by the low bandwidth of visual feedback from high-resolution confocal imaging. The average positioning error was quantified to be 0.4 μm, slightly larger than the Brownian motion–imposed constraint (0.31 μm). The system is also capable of applying a force up to 60 pN with a resolution of 4 pN for a period of time longer than 30 min. The measurement results revealed that significantly higher stiffness exists in the nucleus’ major axis than in the minor axis. This stiffness polarity is likely attributed to the aligned actin filament. We also showed that the nucleus stiffens upon the application of an intracellularly applied force, which can be attributed to the response of structural protein lamin A/C and the intracellular stress fiber actin filaments.

Flexible Ferrofluids: Design and Applications

“…Other Therapeutic Strategy : Aside from the aforementioned ferromagnetic‐particle‐based chemotherapy and hyperthermia therapy, magnetic mechanical agitation and tumor starvation therapy have been proposed in oncotherapy as well . A typical example of magnetic mechanical agitation therapy is based on magnetically responsive nanochains and nanobundles fabricated by Kralj and Makovec .…”

“…As for tumor starvation therapy, magnetically responsive nanorobots which were accurately controlled by multipole magnetic tweezers have been presented currently . It was found that these magnetic nanorobots were swallowed into the living cancer cells under a magnetic field generated by magnetic coils.…”

Automatic Noncontact Extraction and Independent Manipulation of Magnetic Particles Using Electromagnetic Needle

“…Magnetic manipulation of microparticles has attracted tremendous attention during the past two decades [9]- [12]. This technology is appealing because magnetic field allows non-contact manipulation and affects only magnetic particles with little impact on other objects e.g.…”

“…This technology is appealing because magnetic field allows non-contact manipulation and affects only magnetic particles with little impact on other objects e.g. cells [9], [10]. Manipulation using magnetic fields has found a wide range of applications such as sorting and trapping of magnetically tagged micro-organisms [12], [13], sub-cellular control of signaling [14] and immunoassays [15], to name a few.…”

“…However, selective and independent manipulation of particles with the presence of other particles is challenging for the current non-contact magnetic manipulation techniques. For most non-contact magnetic manipulation, the magnetic field is global and it influences all particles in the workspace [9], [24]- [28]. These magnetic manipulation technologies work well when manipulating a single magnetic particle or a swarm of particles.…”