The manipulation of bacteria and mammalian cells through viscoelasticity and acoustofluidics

Open Access
- Author:
- Liao, Wentian
- Graduate Program:
- Biomedical Engineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 01, 2024
- Committee Members:
- William Hancock, Major Field Member
Pak Kin Wong, Major Field Member
Igor Aronson, Chair & Dissertation Advisor
Ayusman Sen, Outside Unit & Field Member
Yuguo Lei, Professor in Charge/Director of Graduate Studies - Keywords:
- Active matter
Viscoelasticity
Collective motion
Acoustofluidics
Cell manipulation - Abstract:
- The manipulation of biological targets like bacteria and mammalian cells has wide biomedical applications, such as drug/cargo transport, in vivo imaging, biofilm removal, purification, sorting, separation, and isolation. In this work, we developed two approaches for manipulating bacteria and mammalian cells. First, we used the intrinsic rheological property of a non-Newtonian medium (mucus), namely viscoelasticity, to control the bacterial collective dynamics. This viscoelasticity manipulation does not require an external energy source such as a magnetic field, ultrasound, or light. Therefore, the setup is much more simplified. We can increase the length scale of collective bacterial locomotion by increasing the mucus's elasticity. The speed of collective motion can be controlled by the viscosity without changing its length scale. The viscoelasticity manipulation is not limited to mucus but applies to a variety of non-Newtonian biological environments, such as blood, saliva, biofilm, liquid crystal, DNA solutions, and extracellular matrix. The experimental observations are supported by computational modelings. Our results provide insight into how medium (mucus) viscoelasticity manipulates the spatiotemporal organization of collective microswimmer dynamics. The finding also sheds light on drug delivery and the spreading of infectious bacteria at the mucosa surface. The viscoelasticity manipulation of bacteria collective dynamics is non-selective, meaning that all cargoes or swimmers in the system, regardless of their size, shape, or surface properties, will move by local collective flows. This limitation restricts its effectiveness, especially on targeted drug/cargo delivery, sorting, and purification where selective manipulation is required. To resolve the limitation on selectivity, we developed a bulk acoustic wave (BAW) acoustofluidic, featuring a nozzle that connects two parallel microchannels with two different widths. This device establishes dominant acoustic resonance and radiation force in the main parallel microchannel. Additionally, the nozzle geometry facilitates secondary acoustic radiation force and acoustic streaming against the bulk fluid flow. By turning acoustic waves on and off, this device enables accumulation, trapping, and extrusion of cells selectively based on their sizes. As the acoustic radiation force scales with the cube of the size of biological targets, the device can accurately manipulate larger targets while smaller targets remain unaffected. Moreover, the pattern of accumulated cells can be controlled by adjusting the frequency and intensity of the acoustic waves. These results present an effective acoustic manipulation, specifically the size-based selective cell extrusion. It has many biomedical applications, such as the purification of pathogen-infected blood, separation of big cancer cells from small normal cells, and bioprinting with cells.