Dynamics, Manipulation and Fluid Flow of Microswimmers, for Applications in Microrheology and Cellular Biophysics

Abstract

Artificial microscale robots carrying out biomedical tasks inside the human body is an important research goal across the entire scientific community. Fuelled by recent advancements in nanotechnology, there has been a tremendous development in the field of micro/nanoscale robots which are pushing the boundaries of biomedical technologies. Due to their small size, they require special strategies to achieve locomotion in fluidic media and, in many cases, these strategies are adopted by mimicking the motion of natural microorganisms like bacteria, algae and spermatozoa. These artificial micro/nanorobots, as we discuss in this thesis, have tremendous potential for future biomedical applications in sensing, targeted delivery, nanosurgery, and detoxification. Powering an artificial micron-scale system is a challenging task, and hence, researchers have been exploring numerous ways to induce motility in these tiny artificial systems, including chemical, magnetic, light and electrical methods. In this thesis, we are going to focus on various applications of magnetically actuated helical microscale objects, termed ‘microswimmers’. Owing to their helical structure, the microswimmers can be maneuvered in any direction in 3D, due to the rotational-translational coupling when it is actuated by a rotating magnetic field. Fabrication of these helical microswimmers requires complex nanofabrication technologies. We have discussed various techniques in detail that we use to fabricate the helical microstructures. We start with a seed layer that decides the thickness of the helix, and therefore, it is important to achieve seed layers of different sizes for varying the thickness of the helices. On the other hand, the height can be controlled as required depending on the amount of deposited materials. Once the helical structures are fabricated, we incorporate a thin magnetic material to render them magnetically active for further experiments. In this thesis, we have explored the possibility of these microswimmers to be used as a microrheological probe. Exquisite control on positioning along with the ability to sense the local rheological properties with high spatio-temporal resolution allows its applicability in the mechanical mapping of a heterogeneous environment. We have utilised the dynamics of a viii microswimmer under rotating magnetic fields in fluidic media to analyse the rheological properties. This technique can be faster than conventional passive microrheology techniques, which can allow the study of rapidly changing environments, for example, mixing of fluids, with very high accuracy. Next, we have attempted to replicate the rheological studies in an intracellular environment, which is a challenging environment undergoing constant reorganisation. We classify our studies along three objectives. We first demonstrated spontaneous internalization and controlled maneuverability of the microswimmers inside living cells. We find similar results in three different cell lines, including cancerous and non-cancerous cells that we use in our experiments confirming the generality of the observations. Thereafter, we have performed detailed studies to understand the physical parameters involved in internalization and expulsion of microswimmers, including direct observation of internalization and expulsion of microswimmers by cells. Finally, we validate how one can sense in the differential intracellular environment from the dynamics of the swimmers. In the following section, we have shown how it is possible to manipulate the entire cell using an internalized microswimmer using magnetic actuation, which is relevant to single-cell manipulation applications. A microswimmer which is capable of maneuvering in an intracellular matrix along with the potential to manipulate an entire cell can open up the possibilities in studies related to phenotype heterogeneity like tumour metastasis, drug resistance, stem cell differentiation, as well as, cell signalling dynamics and targeted therapy. Finally, we have investigated the fluidic interactions of a rotating helix. Basic understanding of fluid flow for a single helix is extremely crucial for the future studies toward many-particle dynamics of a swarm of helices and also understanding magnetically powered artificial active matter system. We have used particle image velocimetry to obtain the fluid profile experimentally around a rotating helix, and the results are supported by numerical simulations and analytical modelling using the singularity solution of Stokes equations.