Available online at [Link].

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Available online at [Link]
ScienceDirect
AvailableScienceDirect
online at [Link]
Procedia Computer Science 00 (2024) 000–000
Procedia Computer Science 00 (2024) 000–000 [Link]/locate/procedia
ScienceDirect [Link]/locate/procedia
Procedia Computer Science 250 (2024) 108–114

Proceedings of the 2024 International Conference on Biomimetic Intelligence and Robotics

Proceedings of the 2024 International Conference on Biomimetic Intelligence and Robotics
Numerical studies of ultrasound-assisted magnetic beads mixing
Numerical studies of ultrasound-assisted
based magnetic
on acoustic streaming effect beads mixing
based on acoustic streaming effect
Chengxi Huanga,b, Yulin Huanga,b, Yang Hua,b, Jianxiong Guana,b, Dongxu Zhanga,b, *
a
Chengxi Huanga,b, Yulin Huanga,b, Yang Hua,b, Jianxiong Guana,b, Dongxu Zhanga,b, *
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, Department
a
State Key Laboratory ofofVaccines
Experimental Medicine,
for Infectious School of
Diseases, Public
Xiang AnHealth, Xiamen
Biomedicine University,Department
Laboratory, Xiamen, 361102, China Medicine, Department
of Laboratory
b
National Institute of Diagnostics and Medicine,
of Experimental Vaccine Development in Infectious
School of Public Health, Diseases, NMPA Key
Xiamen University, Laboratory
Xiamen, for Research
361102, China and Evaluation of
b Infectious
National Institute of Diagnostics andDisease Diagnostic
Vaccine Technology,
Development Xiamen
in Infectious University,
Diseases, NMPA Xiamen, 361102, China
Key Laboratory for Research and Evaluation of
Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, 361102, China

Abstract
Abstract
The rapid development of microfluidics has greatly facilitated the application of magnetic bead in biochemical analysis, where
their rapid
The mixing with reagents
development is a critical step
of microfluidics has to effectively
greatly capture
facilitated the target substances
the application of magneticandbead
directly affect the accuracy
in biochemical of the
analysis, where
results. This with
their mixing research delves
reagents is ainto ultrasound-assisted
critical step to effectively mixing
captureof the
magnetic beads based
target substances and on acoustic
directly streaming
affect [Link] We
the accuracy the
investigate
results. Thistheresearch
acousticdelves
field and
intoacoustic streaming generated
ultrasound-assisted mixing of in the reactionbeads
magnetic chambers
basedmade from three
on acoustic materialseffect.
streaming (PP, PC,We
PMMA)
investigateandthefour structures
acoustic field(spherical,
and acousticcylindrical,
streaming square, EP tubular)
generated and simulate
in the reaction the motion
chambers made process of the
from three magnetic
materials beads.
(PP, PC,
The
PMMA)findings
and of
fourresearch suggests
structures that cylindrical
(spherical, cylindrical,chambers
square, EPandtubular)
square chambers exhibit
and simulate the better
motionmixing
processproperties, especially
of the magnetic [Link]
square chambers
The findings using PMMA
of research suggestsmaterials, with about
that cylindrical 14% ofand
chambers the square
magnetic beads able
chambers to reach
exhibit betterthe planeproperties,
mixing within 0.1 especially
s. For currentthe
chambers
square with better
chambers mixing materials,
using PMMA performance, withPMMA
about 14%material
of themay be a more
magnetic beads favourable material
able to reach choice
the plane withinfor0.1
magnetic beads
s. For current
mixing.
chambersThis with research enhancesperformance,
better mixing the understanding
PMMAofmaterial
ultrasound-assisted
may be a more mixing mechanisms
favourable materialin choice
biochemical reactionsbeads
for magnetic and
provides possible
mixing. This recommendations
research enhances theforunderstanding
chamber structure design and materialmixing
of ultrasound-assisted selection.
mechanisms in biochemical reactions and
© 2024 The
provides Authors.
possible Published by ELSEVIER
recommendations for [Link] design and material selection.
© 2024
This is The
an Authors.
open access Published
article by Elsevier
under the B.V.
CC BY-NC-ND license ([Link]
© 2024 The
This is an openAuthors.
access Published by
article under ELSEVIER
the scientificB.V.
CC BY-NC-ND license ([Link]
Peer-review
This is an under
open responsibility
access article of the
under the CC committee
BY-NC-ND of the
license Proceedings of the 2024 International Conference on
Peer-review Intelligence
Biomimetic under responsibility
and of the scientific committee
Robotics of the([Link]
Proceedings of the 2024 International Conference on Biomimetic
Peer-review under responsibility
Intelligence and Robotics of the scientific committee of the Proceedings of the 2024 International Conference on
Keywords: Numerical
Biomimetic simulation;
Intelligence Acoutic streaming; Particle tracking; Magnetic bead; Mixing
and Robotics
Keywords: Numerical simulation; Acoutic streaming; Particle tracking; Magnetic bead; Mixing

1. Introduction
1. Introduction
With the robust development of microfluidic systems, nanomaterials and nanoparticles have become the focus of
With the robust development of microfluidic systems, nanomaterials and nanoparticles have become the focus of

* Corresponding author. Tel.: 0592-2880660; fax: 0592-2181258.

* E-mail zhangdongxu@[Link]
address:author.
Corresponding Tel.: 0592-2880660; fax: 0592-2181258.
E-mail address: zhangdongxu@[Link]
1877-0509 © 2024 The Authors. Published by ELSEVIER B.V.
This is an open
1877-0509 access
© 2024 Thearticle under
Authors. the CC BY-NC-ND
Published by ELSEVIER license
B.V.([Link]
Peer-review under
This is an open responsibility
access of the
article under the scientific
CC BY-NC-NDcommittee of the
license Proceedings of the 2024 International Conference on Biomimetic Intelligence
([Link]
and Roboticsunder responsibility of the scientific committee of the Proceedings of the 2024 International Conference on Biomimetic Intelligence
Peer-review
and Robotics
1877-0509 © 2024 The Authors. Published by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license ([Link]
Peer-review under responsibility of the scientific committee of the Proceedings of the 2024 International Conference on
Biomimetic Intelligence and Robotics
10.1016/[Link].2024.11.016
 Chengxi Huang et al. / Procedia Computer Science 250 (2024) 108–114 109
2 C. Huang et al. / Procedia Computer Science 00 (2024) 000–000

research [1], especially particles with superparamagnetic properties, which are commonly referred to as magnetic
beads [2]. By chemically modifying the surface to attach different molecules such as antibodies, proteins or nucleic
acid, magnetic beads are able to specifically capture the target substances, which allows for rapid and accurate
enrichment or separation of the target substance in complex biological samples. Magnetic beads have been
recognized as a standard tool for the specific attachment of biomolecules for detection, analysis, and quantification
purposes [3]. Magnetic beads expand the functionality of microfluidic systems and improve their application
prospects in the fields of cell manipulation[4], molecular diagnostics[5] and drug delivery [6]. During the reaction
process, the mixing of magnetic beads and biological reagents is inevitable, which is a critical step to effectively
capture the target substances and directly affect the accuracy of the results. However, the flow state in microfluidic
systems usually manifests as laminar flow, resulting in slow mixing speed of magnetic beads and reagents [7],
which is often fail to meet the requirements of biochemical reactions. Therefore, it is necessary to rely on external
driving forces, such as electricity[8], magnetism [9], heat [10], acoustic waves [11], to accelerate the mixing process.
Acoustic waves, with its non-invasive propagation mechanism, have been widely used in the microfluidics. It can
achieve various functions, such as fluid mixing [12], particle manipulation [13], and acoustic aggregation [14] and
generate multiple effects, such as acoustic streaming [15], cavitation [16], and thermal effect [17]. Acoustic
streaming refers to the fluid flow generated by the attenuation of acoustic waves in a fluid, which is classified into
two common types: boundary-driven streaming and bulk-driven streaming. The former, also known as Schlichting
streaming, results from the dissipation of acoustic energy due to the large velocity gradient in the viscous boundary
layer [18]. The latter, also known as Eckart streaming, is due to the viscous dissipation of acoustic waves within the
fluid and this energy loss produces a steady jet in the direction of acoustic wave propagation [19].
Lim et al [20] introduced a dome-shaped chamber-based SAW (DC-SAW) device, which showed a mixing index
higher than 90% at both 20 V and a flow rate of 300 μL/min. Rasouli et al [21] developed an energy-efficient
acoustic platform based on boundary-driven streaming, which utilizes strong vortices generated by oscillating
bubbles and sharp edges to achieve rapid mixing of controlled nanoparticle precipitates. However, one of the major
challenges of microfluidic chips for mixing applications is that their fabrication relies on sophisticated and complex
machining techniques, which limits their possibilities for mass production and widespread application. Plastics are
widely used in microfluidics due to their good biocompatibility and optical properties as well as their low cost and
easy manufacturing [22]. Currently, injection molding is the most widely used plastic fabrication method in industry
[23], enabling high throughput fabrication at low cost while maintaining tight tolerances and high reproducibility
[24]. Based on the concept of microfluidics, Cepheid concentrated the reaction reagents into a sealed chamber, and
assisted the nucleic acid extraction by the ultrasound transducer acting with the chamber. However, Cepheid did not
give the mechanism of ultrasound action. Zhang et al. [26] proposed an ultrasound-assisted NAE method combining
acoustic streaming effect and the magnetic bead method. An external ultrasound transducer interacting with the
chamber structure was used to achieve efficient mixing of magnetic beads and reagents. The acoustic streaming
effect was further enhanced by optimizing the incidence angle of ultrasound and the microstructure design inside the
chamber to facilitate the mixing of magnetic beads and biological reagents.
In this research, the acoustic flow effects generated in chambers of different structures and materials are
investigated through numerical simulations, aiming to optimize the mixing efficiency of magnetic beads and
reagents within a solid-fluid system. We firstly calculates the steady-state acoustic field generated by the interaction
of the ultrasonic transducer and the chamber, and then substances the acoustic streaming effect excited in different
chambers. The motion of the magnetic beads in the flow field was further observed by particle tracking to assess the
overall mixing effect. This research enhances the understanding of ultrasound-assisted mixing mechanisms in
biochemical reactions and provides possible recommendations for chamber structure design and material selection.

2. Numerical simulation

2.1. Geometric model

The structure of the reaction chamber is shown in Fig. 1a. The ultrasonic transducer is replaced by a simplified
ultrasonic head, which is tangent to the bottom of the chamber and its axis coincides with the z-axis. The capacity of
the chamber is 500 μL, filled with liquid inside and and is filled with biological reagents inside and evenly
110 Chengxi Huang et al. / Procedia Computer Science 250 (2024) 108–114
C. Huang et al. / Procedia Computer Science 00 (2024) 000–000 3

distributed with magnetic beads at the bottom. Four common structures were designed: spherical chamber,
cylindrical chamber, square chamber, and EP tube chamber. Fig. 1b-e represents the cross-section of the four
structures in the y-z direction, and the specific dimensions of each structure are shown in Table 1. Three
thermoplastic materials commonly used in industry for injection molding process are selected for the chambers,
namely Polypropylene (PP), Polycarbonate (PC), and Polymethyl Methacrylate (PMMA), and the ultrasonic head is
made of stainless steel, and the biological reagents are replaced by water.

Fig. 1 Geometric model: (a) Schematic diagram of the reaction chambers; Cross-section in y-z direction: (b) spherical; (c) cylindrical; (d) square;
(e) EP tubular

Table 1 Reaction chamber model dimensions

Ref Dimension Ref Dimension

L 15mm h 5 mm
W 2mm d 1.75 mm
T 1mm l1 5.1 mm
R 6.2mm l2 4.5 mm
H 6.2mm l3 4.4 mm

2.2. Governing equations

Comsol Multiphysics 6.2 is used to simulate the ultrasound-assisted mixing process of magnetic bead particles.
Considering the viscous dissipation effect in the actual propagation of acoustic waves, the acoustic field is modeled
using thermo-viscous acoustics, and the governing equations [27] can be expressed as:

∂ t T1 = Dth ∇ 2T1 +
α T0
∂ p (1)
ρ0C p t 1

p1
∂t=
1
[α∂ t T1 − ∇ ⋅ v1 ] (2)
γκ

ρ0 ∂ t v1 = −∇p1 + η∇ 2 v1 + βη∇(∇ ⋅ v1 ) (3)

Here, Dth is the thermal diffusivity, η is the dynamic viscosity, β is the viscosity ratio; T0 is constant temperature,
ρ0 is the density; T1, p1, v1 are, respectively, the first-order temperature, pressure, and velocity. Cp is the specific heat
 Chengxi Huang et al. / Procedia Computer Science 250 (2024) 108–114 111
4 C. Huang et al. / Procedia Computer Science 00 (2024) 000–000

capacity at constant pressure; γ is the specific heat capacity ratio; κ is the isentropic compression coefficient, and α
is the isentropic thermal compression coefficient.
Assuming all first-order fields have harmonic correlations e-iωt that are inherited from the applied ultrasound field,
the above governing equation can simplify as:
γ −1 (4)
iωT1 + γDth ∇=
2
T1 ∇ ⋅ ν1
α

 1  α (5)
iω v1 + ν∇ 2 v1 + ν  β + i  ∇(∇ =
⋅ ν1 ) ∇T1
 γρ 0 κνω  γρ 0κ

Here, ν = η/ρ0. The thermal effects that arise in the thermoviscous equations described above are of secondary
importance for water and most liquids. To simplify the calculations, the thermal effects are introduced only through
the temperature-dependent first-order fields ρ1 and v1.
In order to establish the relationship between the acoustic field and the flow field in the numerical model, the
action of the acoustic field on the fluid is added to the momentum equation of the fluid by means of volumetric
forces [28] to solve for the acoustic flow field for the flow velocity v2. The expression for the volumetric forces is
given by:

1 1   ∂u   ∂u   ∂u  
F= Re  ρe∗ω u  + ρe  Re u x∗  + Re u ∗y  + Re u z∗   (6)
2 2   ∂x   ∂y   ∂z  
Here, ρe∗ is the complex conjugate of density perturbation, u the particle velocity and its components ux, uy, uz in
cartesian coordinate system.

2.3. Model descriptions and boundary conditions

In the numerical modeling, the steady state acoustic field, acoustic streaming flow field, and the motion of the
magnetic beads generated in the chamber are observed by applying ultrasonic action with a vibration frequency of
40 kHz and an amplitude of 10 μm to chambers of different structures and materials. The material properties of
water are taken from comsol material library. The magnetic beads have a density of 1060 kg/m3 and a particle
diameter of 2 μm. Other material parameters are shown in the table below:

Table 2 Material properties

PP PC PMMA Stainless steel
Density 900kg/m3 1200kg/m3 1190kg/m3 7930kg/m3
Young's modulus 1.75Gpa 2.32Gpa 3Gpa 193Gpa
Poisson's ratio 0.42 0.39 0.4 0.3
Wave velocity 1394m/s 1390m/s 1588m/s

In order to simplify the calculation, a 1/4 model is used with symmetric boundaries on both sides, and the rest of
the boundary conditions are set as shown in Fig. 2 below:

Fig. 2 Schematic diagram of boundary conditions

112 Chengxi Huang et al. / Procedia Computer Science 250 (2024) 108–114
C. Huang et al. / Procedia Computer Science 00 (2024) 000–000 5

3. Results and discussions

The acoustic field distribution in the fluid domain is the primary concern. Since the ultrasonic frequency is very
high and the period is very short, according to the wavelength formula λ = c/f0, the wavelength of ultrasonic wave in
water is 37.5 mm, which is much larger than the size of the reaction chambers, so the stable acoustic pressure
distribution can be obtained within 1s of ultrasonic action. Fig. 3a-d represents the results of the acoustic pressure
field distribution in the fluid domain in reaction chambers of different structures and materials. The structure and
material of the reaction chambers can lead to significant changes in the acoustic pressure field distribution inside,
producing different acoustic wave propagation patterns. The acoustic pressure values at the center intercept of each
surface in Fig. 3a-d were extracted, as shown in Fig. 4a-d.

Fig. 3 Acoustic field distribution in the Y-Z plane: (a) spherical; (b) cylindrical; (c) square; (d) EP tubular

Fig. 4 Acoustic pressure value curves at the center intercept: (a) spherical; (b) cylindrical; (c) square; (d) EP tubular

The cylindrical and square chambers have a stronger acoustic pressure field and may be able to induce more
intense acoustic streaming compared to the spherical and EP tubular chambers. The reason for the above
phenomenon may be that the cylindrical and square chambers provide a larger contact area with the ultrasonic head
to achieve face-to-face contact, which leads to more intense vibrations. In the cylindrical and square chambers,
using PMMA material exhibits a larger gradient of acoustic pressure and has a higher acoustic pressure at the
bottom than at the top. This indicates that the propagation pattern of acoustic waves is bottom-up, which is more
suitable for magnetic beads mixing. Different structures and materials produce different acoustic fields and thus
excite different flow patterns. Since the acoustic pressure field is stable, the flow field will reach a steady state in a
very short time. Fig. 5a-d represents the flow field distributions for x = -1 mm and y = -1 mm sections. (Unit: mm/s).

Fig. 5 Flow field distributions in x = -1 mm and y = -1 mm sections (a) spherical; (b) cylindrical; (c) square; (d) EP tubular
 Chengxi Huang et al. / Procedia Computer Science 250 (2024) 108–114 113
6 C. Huang et al. / Procedia Computer Science 00 (2024) 000–000

The spherical chambers have stronger flow on both sides, while the EP tubular chambers have stronger flow on
both sides as well as in the center. The common feature of both chambers is that the flow pattern is from the center
to the ends (top and bottom) and shows a clockwise flow. The flow velocity in the region of concentration of
magnetic beads at the bottom is relatively slow in both chambers. The flow patterns of the cylindrical and square
chambers show more complexity, producing obvious spatial vortices. And these two chambers produce stronger
flow at the bottom, which is favourable to drive the magnetic beads. In contrast, the flow at the top of the square
chamber is stronger than that of the cylindrical chambers. In terms of material selection, the overall flow rate was
faster when PP material was used for the spherical chambers, and when PMMA material was used for the other
chambers. In particular, the flow rate is much greater when PMMA is used for the cylindrical and square chambers
than for the other materials. It may be due to resonance, which results in a high acoustic pressure inside the
chambers, which excites a extremely strong acoustic streaming.
In the particle tracking module, a certain number of magnetic beads are placed at the bottom of the chambers
through a grid. The magnetic beads are driven by acoustic streaming and their movement in the liquid is observed.
In order to roughly assess the mixing efficiency of the system, a plane is set in the Z-direction of the fluid domain at
a distance of 1/6 of the total height of the upper surface. Count the percentage of the number of magnetic beads that
cross the plane in 2 s as shown in Fig. 6. (Do not double-count magnetic beads that repeatedly cross the plane due to
vortices).

Fig. 6 Percentage of the number of magnetic beads (a) spherical; (b) cylindrical; (c) square; (d) EP tubular

The above results show that EP tubular chambers are less effective in mixing because of their slower flow rates
and longer mixing times. And probably due to its longer structure, almost no particles are able to reach the set plane,
which resulted in the magnetic beads hardly mixing with the reagents at the top. In other chambers, the magnetic
beads reach the plane in a very short time, which meets the need for rapid mixing. The chambers with PMMA
materials exhibit better mixing properties compared to the chambers with other materials, except for the ep tubular
chambers. In particular, the square chamber with PMMA material exhibits excellent mixing performance, with
about 14% of the magnetic beads able to reach the plane within 0.1 s.

Conclusion

We investigate ultrasound-assisted magnetic bead mixing based on acoustic streaming effect. Firstly, we
calculate the steady state acoustic field generated in the reaction chambers of three materials (PP, PC, PMMA) and
four structures (spherical, cylindrical, square, EP tubular). Then we calculate the acoustic streaming field excited by
the acoustic field and simulate the motion process of the magnetic beads by a particle tracking model. It is found
that cylindrical chambers and square chambers exhibit better mixing properties, especially the square chambers
using PMMA materials, with about 14% of the magnetic beads able to reach the plane within 0.1 s. For current
chambers with better mixing performance, PMMA material may be a more favourable material choice for magnetic
beads mixing. This research enhances the understanding of ultrasound-assisted mixing mechanisms in biochemical
reactions and provides possible recommendations for chamber structure design and material selection.

Acknowledgements

This work was supported by Medical Research Program Project of Fujian Provincial Health and Wellness
Commission (2021ZD01006), Key Research and Development and Conversion Plan of Inner Mongolia
Autonomous Region (2023YFDZ0060) and Xiamen Huli District Maternal and Child Care Hospital – Horizontal
Project (20223160A0463).
114 Chengxi Huang et al. / Procedia Computer Science 250 (2024) 108–114
C. Huang et al. / Procedia Computer Science 00 (2024) 000–000 7

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