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2023 IEEE 7th Portuguese Meeting on Bioengineering (ENBENG)

22-23 June, 2023. Porto, Portugal

A Numerical Study of the Heat Distribution


Generated by a Microheater in an Organ-on-a-Chip
Chamber
Gabriel M. Ferreira Paulo J. Sousa Vânia C. Pinto
Microelectromechanical Systems Microelectromechanical Systems Microelectromechanical Systems
Research Unit (CMEMS-UMinho), Research Unit (CMEMS-UMinho), Research Unit (CMEMS-UMinho),
LABBELS—Associate Laboratory, LABBELS—Associate Laboratory, LABBELS—Associate Laboratory,
2023 IEEE 7th Portuguese Meeting on Bioengineering (ENBENG) | 979-8-3503-2257-6/23/$31.00 ©2023 IEEE | DOI: 10.1109/ENBENG58165.2023.10175328

University of Minho, INL-International University of Minho University of Minho


Iberian Nanotechnology Laboratory Braga, Portugal Braga, Portugal
Braga, Portugal psousa@dei.uminho.pt vpinto@dei.uminho.pt
id10786@alunos.uminho.pt
Patrícia C. Sousa Graça Minas
Susana O. Catarino INL-International Iberian Microelectromechanical Systems
Microelectromechanical Systems Nanotechnology Laboratory, Research Unit (CMEMS-UMinho),
Research Unit (CMEMS-UMinho), Braga, Portugal LABBELS—Associate Laboratory,
LABBELS—Associate Laboratory, patricia.sousa@inl.int University of Minho
University of Minho Braga, Portugal
Braga, Portugal gminas@dei.uminho.pt
scatarino@dei.uminho.pt

Abstract— In an organ-on-a-chip (OoC), temperature must be and physiological behaviour of human tissues and organ
kept stable for a well-controlled and human representative models [1]. In particular, such microdevices have been
microenvironment. This work presents the numerical simulation of explored in the area of cancer therapeutics, to help predict the
a microheater to be integrated in a polydimethylsiloxane chamber new drugs response. These devices require the control of
that will comprise an OoC. Numerical simulations were performed several parameters for the suitable cell culture growth
to evaluate the heat distribution, considering the fluid flow and its assuring a controlled and realistic microenvironment of the
direction, the microheater and substrate materials, and the thickness cells, such as temperature, pH, oxygen, CO2, glucose and
of the oxide layer (electric insulator), on top of the microheater.
lactase concentration [2], [3], [4]. When healthy and tumoral
Silicon (Si) and glass for the substrate, and platinum (Pt) and
organ models are used inside an OoC, with an integrated
aluminium (Al) for the microheater materials were evaluated.
Results showed that the Si substrate assured better heat uniformity
sensing and actuation system, it will be possible to identify,
than glass, although reaching lower temperature values, for the same quantify and control with high sensitivity, at real-time and in-
input power. For the microheater, although Al achieved better heat situ the physicochemical parameters released during
uniformity than Pt, it needed higher current to reach the same chemotherapy assays. This precise monitoring is of utmost
temperatures (ranging from 35-45°C). The oxide layer thickness did importance for the prediction of the therapeutic drugs effect,
not affect the achieved temperature. The Si substrate/Pt microheater elucidating the role of individual variables, advantaging
microsystem was able to heat the fluid chamber up to the 35-45ᵒC speed, control, reproducibility and cost, in order to reduce,
range, with current consumption from 0.06 A to 0.1 A, respectively, refine and replace animal testing. For this application, the
showing good heat uniformity and low power consumption. OoC system must be able to operate in a target temperature
Regarding the fluid flow, the domain temperature decreases as the ranging 35°C to 45°C, in order to cover the optimal cell
flow rate increases, for the same actuation conditions. It was also growth temperatures, as well as hypothermia and
analysed the effect of the flux direction and it was observed that, at hyperthermia situations [5], [6].
120 µL/min, it did not affect the heat distribution in the chamber.
Therefore, for a well-controlled microenvironment, it was
Keywords—Organ-on-a-chip, temperature, microheater, designed and simulated (using COMSOL Multiphysics
COMSOL Multiphysics software. software) a microheater system to study the heat distribution
inside a polydimethylsiloxane (PDMS) microfluidic
I. INTRODUCTION microchamber that comprises the cultured cells, representing
In order to better control and predict drug performance in in the OoC. The microheater was designed to be integrated into
vitro studies, the concept of organ-on-a-chip (OoC) has been the circular culture microchamber, as showed in Fig. 1.
increasingly addressed. These microdevices are described as The heating system was based on the joule effect, by applying
new microfluidic devices capable of simulating the biological an electric current circulating in a conductive material [7].

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Thus, this article presents the study of: the influence of the 𝜕𝑇 (7)
microheater and the substrate materials; the thickness of the 𝜌𝐶𝑝 ( + 𝑢 . ∇𝑇) + ∇ . (𝑞 + 𝑞𝑟 )
𝜕𝑡
insulating oxide layer; the applied current; and the liquid flow 𝜕𝑝
parameters, on the temperature distribution inside the PDMS = 𝛼𝑝 𝑇 ( + 𝑢. ∇𝑝) + 𝜏: ∇𝑢 + 𝑄
𝜕𝑡
chamber. where ρ (kg/m3) is the material density, Cp (J/(kg.K)) is the
solid heat capacity at constant pressure, u (m/s) represents the
velocity field, T (K) is the temperature, q is the heat flux by
conduction (W/m2), qr is the heat flux by radiation (W/m2), S
is the second Piola-Kirchhoff stress tensor and Q (W/m3) is
the heat source (or sink). QTed represents the thermoelastic
damping, which accounts for the thermoelastic effects in
Fig. 1. Schematic representation of the microheater integrated in the organ- solids, p is the coefficient of thermal expansion (1/K) and 𝜏
on-a-chip chamber. is the viscous stress tensor (Pa). Regarding the boundary
conditions, convective heat flux (external natural convection)
II. METHODS was defined in the chamber walls and in the substrate
A. Numerical model boundaries. The pressure and temperature initial conditions
were considered as 1 atm and 20ºC, respectively.
COMSOL Multiphysics software (version 5.3), based on
finite element analysis, was used to perform the numerical Finally, the laminar flow interface is characterized by the
simulations. To model the microheater, the numerical model Navier-Stokes continuity (equation 9) and momentum
took into account the physical equations of different (equation 10) equations [10]:
phenomena: (1) heat transfer in solids and fluids; (2) electrical
𝜌 𝛻.u = 0 (9)
current applied to the microheater (electric currents, shell
module); (3) fluid flowing through the chamber (laminar flow 𝜌
𝜕𝑢
+𝜌(u. 𝛻)u=𝛻. [−𝑝I+µ (𝛻𝑢 + (𝛻𝑢)𝑇 )] +F (10)
module). Additionally, three multiphysics modules were 𝜕𝑡
added to establish the connection between the referred where ρ is the density (kg/m3), u is the velocity vector (m/s),
physical equations: Boundary Electromagnetic Heat Source, p is pressure (Pa), I the identity matrix, μ the viscosity (Pa.s)
Temperature Coupling and Flow Coupling Multiphysics. and F is the volume force vector (N/m3). Regarding the
In the electric current model, an input current was defined to boundary conditions, a flow rate was defined in the inlet
flow in the microheater through the terminal pads. Due to the boundary, the outlet was defined as zero pressure and the
joule effect, the structure of the microheater, with 200 nm chamber walls as zero velocity.
thickness, undergoes heating. For the electric current
B. Geometry and materials
interface, the main equations are the following [8]:
The OoC circular chamber was designed in a 3D domain, as
∇. 𝐽 = 𝑄𝑗 (1) shown in Fig. 2a. The PDMS chamber has a 3 mm height and
𝐽 = 𝜎𝐸 + 𝐽𝑒 (2) a 4 mm radius. The substrate presents a 600 µm thickness.
The microheater structure (Fig. 2b) was designed as a long
𝐸 = −∇𝑉 (3)
thin film with lines varying between 0.30 mm and 0.48 mm
2
where 𝐽 is the current density (A/m ), 𝑄𝑗 is the external width, with 200 nm thickness. Two materials were simulated:
current source, 𝜎 is the electrical conductivity (S/m), Je is the aluminium and platinum. Their resistivity (𝜌0 ) at 20ᵒC and
externally generated current density (A/m2), E is the electric temperature coefficient of resistance (α) are presented in table
field (V/m) and V (V) is the electric potential. The I. It was also defined the fluid (water), the inlet and the outlet
temperature-dependent conductivity is described by: regions (Fig. 2a), as well as the contact pads of the
1 (4) microheater, as shown in Fig. 2b, where one represents the
𝜎= ground and the other is the applied current terminal. The
𝜌0 (1 + 𝛼(𝑇 − 𝑇𝑟𝑒𝑓 )) mesh includes 2214539 tetrahedral elements.
where 𝜌0 is the resistivity at the reference temperature Tref
(K), α is the temperature coefficient of resistance and T (K) is
the temperature. In the heat transfer in solids interface, a thin
200 nm thickness metal layer was defined, responsible to
generate heat through the chamber and fluid. The main
equations that describe the heat transfer in solids [9]
Fig. 2. (a) Complete geometry of the organ-on-a-chip chamber (gray
(equations 5 and 6) and fluids (equations 7 and 8) are:
domain) with the microheater (black boundary) on a substrate (orange
𝜕𝑇 𝑑𝑆 (5) domain). Blue arrows represent the flow direction. (b) Top view (XY plane)
𝐶𝑝 ( + 𝑢𝑡𝑟𝑎𝑛𝑠 . ∇𝑇) + ∇ . (𝑞 + 𝑞𝑟 ) = −𝛼𝑇: +𝑄 of the microheater geometry inside the PDMS chamber.
𝜕𝑡 𝑑𝑡
𝑑𝑆 (6) TABLE I. MICROHEATER MATERIAL PROPERTIES
𝑄𝑇𝑒𝑑 = 𝛼𝑇:
𝑑𝑡 Material 𝝆𝟎 (Ω.m)  (1/K)
Aluminium (Al) 2.650E-8 0.00429
Platinum (Pt) 12.447E-8 0.00385

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C. Parameters under study
In the microheater, several values for the applied electrical
current were set to reach temperatures in the fluid ranging
between 35ᵒC to 45ᵒC, according to the different materials
simulated. Furthermore, the temperature variation was
studied for different fluid flow rates: 80, 120 and 300 µL/min
and different flow directions. It was also simulated the
thickness effect of an oxide layer on top of the substrate.
Here, silicon dioxide (SiO2) was used due to be an electrical
insulator and a good thermal conductor, so it is expected not
to affect the heating of the fluidic microchamber. All the
performed simulations are presented in table II.

TABLE II. MICROHEATER AND SUBSTRATE MATERIALS, OXIDE


THICKNESSES AND FLUID FLOW RATES SIMULATED IN COMSOL
MULTIPHYSICS

Oxide Fig. 3. Average temperature of fluid as a function of the applied current in


Flow rate each microheater, for flow rates of 80, 120 and 300 µL/min, considering
Microheater Substrate Thickness
(µL/min) glass and Si substrates and Pt and Al microheaters.
(nm)
No oxide
200 80, 120,
500
Silicon (Si) 300
Platinum (Pt) 1000
8000
Glass No oxide 120
Aluminium 80, 120,
Silicon (Si) No oxide
(Al) 300 Fig. 4. Heat distribution, in a XY plane, 1 mm above the substrate, generated
by a Si+Pt microheater, powered with a current of 0.07 A, for 80, 120 and
III. RESULTS AND DISCUSSION 300 µL/min flow rates. The arrow represents the flow direction.

Fig. 3 presents the average temperature inside the chamber


for different applied electric currents (ranging from 0.06 A to
0.1 A), for platinum and aluminium microheaters and silicon
and glass substrates, for each flow rate presented in table II
(80, 120 and 300 µL/min). It is possible to compare the effect
of the substrate and microheater materials on the temperature
of the fluid inside the chamber. As expected, the temperature
decreases when the fluid flow increases. In Fig. 4 and 5, it is
visualized the heat distribution, 1 mm above the substrate
(Fig. 4) and the 3D heat distribution (Fig. 5) of the Si+Pt
Fig. 5. 3D heat distribution, generated by a Si+Pt microheater, when a 0.07
microheater, for each fluid flow rate, when a current of A current is applied, for 80, 120 and 300 µL/min flow rates. The arrow
0.07 A was applied. In both figures it is possible to observe a represents the flow direction.
greater heat drag with a 300 µL/min flow, i.e., as the flow rate
increases, the convective heat flux also increases, leading to
a higher temperature dissipation and consequently lower
temperature in the chamber area.
The substrate and microheater materials also affect the heat
distribution, as presented in Fig. 6. Due the high thermal
conductivity of silicon (34 W/m.K) in comparison with silica
glass (1.38 W/m.K), the heat distribution of silicon is more
uniform. Although, the glass substrate reaches higher
temperatures, the silicon substrate generates a greater
uniformity of heat distribution generated in the chamber
fluid. As previously observed in Fig. 3, the microheater
material also influences the fluid temperature. The
aluminium microheater reaches lower temperature values due
to the low electrical resistance of the aluminum. However, it Fig. 6. Substrate heat distribution, in the XY plane, for a 0.07 A current
has better heat uniformity than platinum, as demonstrated in applied in the microheaters, at a 120 µL/min flow rate, using: Glass substrate
Fig. 6. and Pt microheater; Silicon substrate and platinum microheater; Silicon
substrate and aluminum microheater.

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In addition to the substrate and microheater materials, the chip chamber with CMOS electronics, capable of controlling
oxide thickness was also studied for the platinum microheater the microheater and featuring other relevant sensors
in a silicon substrate. However, for the simulated thicknesses (including temperature) [6].
(see table II), the resultant temperatures only differed below
0.01ºC and, thus, the results did not show significant ACKNOWLEDGMENT
differences. This work has been supported by the project PTDC/EEI-
Finally, due the position of the pads, the heat distribution EEE/2846/2021 and partially by 2022.02165.PTDC, through
could be affected by the fluid direction. Hence, the fluid flow national funds (OE), within the scope of the Scientific
was inverted in order to understand its influence on the heat Research and Technological Development Projects (IC&DT)
distribution. In Fig. 7, it is presented the temperature program in all scientific domains (PTDC), through the
distribution for two different possible flow directions. As Foundation for Science and Technology, I.P. (FCT, I.P). The
demonstrated for the 120 µL/min flow, the flux direction does authors also acknowledge the partial financial support within
not present significant differences in the obtained heat the R&D Unit Project Scope: UIDB/04436/2020. Gabriel M.
Ferreira thanks FCT for his Ph.D. grant with reference
distribution.
2022.10519.BD. Paulo Sousa, Vânia Pinto and Susana
Catarino thank FCT for their contracts funding provided
through 2021.01086.CEECIND, 2021.01087.CEECIND and
2020.00215.CEECIND, respectively.
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