Optimisation of Acoustic Manipulation for Single Cell Manipulation

Abstract

In microfluidic systems, resonant acoustic fields enable controlled particle manipulation, a phenomena known as acoustophoresis. These contactless and low-cost processes have successfully been applied to manipulate bulk particle populations, however robust single-cell manipulation for single-cell analysis remains a challenge.
This work presents an experimental investigation into optimising the controllability of an acoustofluidic manipulation platform through comparison of different algorithmic control approaches under varying experimental parameters. The study identified voltage as a critical parameter governing a trade-off between manipulation speed and controllability, with an optimal operating regime required to achieve reliable single-cell control.
Different control strategies were evaluated using polystyrene particles and living cells. While the state-of-the-art epsilon-greedy algorithm showed limited performance, a novel adaptive approach based on model predictive control achieved a 100% success rate after optimisation, enabling highly controllable single-cell manipulation. In addition, the results highlight the importance of temporally structured actuation for stable particle trajectories and demonstrate robust performance of the proposed approach, even for more complex manipulation tasks.
These findings establish the feasibility of employing local optimisation, driven by reinforcement learning, for acoustofluidic single-cell handling and represent a promising step towards advanced single-cell analysis and other biomedical applications. Additionally, as a first step toward future controllability approaches, a field‑characterisation procedure was developed and performed to analyse the modal responses of acoustofluidic devices. The method employed a prototype acoustofluidic platform where numerical simulations were combined with experiments encompassing 1) viewing spatial distributions of tracer particles and 2) laser Doppler vibrometry. The resulting insights allowed characterisation the acoustic behaviour, intend to allow further decision informed development of the platform.

Popular Abstract

The Acoustic Multimodal Navigation System: Steering and Delivering Cells With Sound

What if a single living cell could be moved using nothing but sound? This project explores acoustic steering—tiny devices that use sound waves to precisely steer the navigation of living cells without touching them.

The work focused on solving a major challenge in the field: while sound can be used to manipulate a bulk of particles in fluids, controlling one single cell reliably has remained difficult. The aim of this project was therefore to optimise an acoustofluidic manipulation platform to achieve robust single-cell control.
The device works by generating carefully tuned standing sound waves inside a microfluidic chip filled with liquid. These sound waves create invisible pressure patterns that can push or trap particles. Instead of relying only on the sound field itself, this project combined acoustics with a smart feedback control system that continuously tracks a particle’s position and adjusts the sound in real time to guide it toward a chosen target.

A central part of this work was evaluating how different control strategies influence system performance. Existing systems are vulnerable to changes in the system such as nonlinearities and alternations of the acoustic pressure fields. In contrast, this project showed that an adaptive deterministic control algorithm that makes decisions on the go, in a structured and reliable way, performs better. The result was a major improvement in controllability, transforming an unreliable prototype into a robust system capable of manipulating living cancer cells.

An important outcome of the project was the first demonstration of deterministic single-cell control using bulk acoustic standing waves combined with closed-loop feedback. In simple terms, this means a single living cell could be guided predictably using sound alone—something that had not previously been shown.
The work also revealed that successful control depends strongly on finding the right balance between experimental parameters, particularly the strength and timing of the acoustic actuation. Too much force caused cells to move too coarsely, while too little force made manipulation ineffective. By identifying an optimal operating regime, reliable control became possible.

To further improve the system, the project also investigated how different sound resonances inside the device could be measured and combined. By comparing computer simulations with experiments, it became possible to better understand the “sound landscape” inside the chip and use this knowledge to improve particle trapping and positioning.

Why does this matter? The ability to control single cells is increasingly important in modern medicine and biotechnology. Future lab-on-a-chip devices may use technologies like acoustic steering for single cell analysis: probing different features of individual cancer cells.

By showing that single cells can be controlled reliably using sound, this project takes an important step toward making these future technologies possible.

• author: Hevelius Bounja, Selma
• supervisor: Thierry Baasch
• organization: Division for Biomedical Engineering
• alternative title: Optimering av Akustisk Manipulation för Manipulation av Enstaka Celler
• course: BMEM01 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: Acoustofluidics, microfluidics, lab on a chip, single cell analysis, control algorithms, cell manipulation
• language: English
• additional info: 2026-06
• id: 9225942
• date added to LUP: 2026-05-26 13:17:25
• date last changed: 2026-05-26 13:17:25