Controlled Manipulation and Active Sorting of Particles Inside Microfluidic Chips Using Bulk Acoustic Waves and Machine Learning

Abstract

Manipulation of cells, droplets, and particles via ultrasound within microfluidic chips is a rapidly growing field, with applications in cell and particle sorting, blood fractionation, droplet transport, and enrichment of rare or cancerous cells, among others. However, current methods with a single ultrasonic transducer offer limited control of the position of single particles. In this paper, we demonstrate closed-loop two-dimensional manipulation of particles inside closed-channel microfluidic chips, by controlling the frequency of a single ultrasound transducer, based on machine-vision-measured positions of the particles. For the control task, we propose using algorithms derived from the family of multi-armed bandit algorithms. We show that these algorithms can achieve controlled manipulation with no prior information on the acoustic field shapes. The method learns as it goes: there is no need to restart the experiment at any point. Starting with no knowledge of the field shapes, the algorithms can (eventually) move a particle from one position inside the chamber to another. This makes the method very robust to changes in chip and particle properties. We demonstrate that the method can be used to manipulate a single particle, three particles simultaneously, and also a single particle in the presence of a bubble in the chip. Finally, we demonstrate the practical applications of this method in active sorting of particles, by guiding each particle to exit the chip through one of three different outlets at will. Because the method requires no model or calibration, the work paves the way toward the acoustic manipulation of microparticles inside unstructured environments.

Programmable assembly of particles on a Chladni plate

“…Because particles of different sizes and materials will move differently on the same vibrating plate, e.g., toward nodal lines or antinodes, our method can potentially be extended to simultaneously assemble two different types of particles. Beyond the Chladni plate, our approach may be applicable to similar systems exhibiting spatially nonlinear and stochastic dynamics, such as systems with turbulent flow fields ( 31 , 32 ) or microfluidic systems with bulk acoustic waves ( 33 ). Furthermore, our method may inspire novel fabrication technologies and applications in cell and particle sorting based on sequences of external force fields rather than on field- or template-based energy minimization and force balance.…”

Application of Microfluidics in Detection of Circulating Tumor Cells

“…Manipulating cells, droplets, and particles by sound waves in microfluidic chips is a rapidly developing field that is widely used in cell and particle sorting, blood separation, droplet transportation, and rare or cancer cell enrichment ( Yiannacou and Sariola, 2021 ). Wu et al (2018) realized the sorting of CTCs in peripheral blood by using surface acoustic waves ( Figure 3C ), adding sound field and surface acoustic wave sensor according to the arrangement of cells with different sizes, densities, and shapes in the standing wave field.…”

Three-dimensional heating and patterning dynamics of particles in microscale acoustic tweezers

“…They were particularly demonstrated for cell sorting, mostly combined with a microfluidic flow-through system. [21][22][23][24] In contrast, acoustic tweezers based on the primary excitation of surface acoustic waves (SAW) allow efficient manipulation with even smaller acoustic wavelengths. Moreover, complex acoustic fields can be realized by superposition of several SAWs facilitating a more precise cell manipulation, e.g.…”