Towards CMOS Integrated Microfluidics Using Dielectrophoretic Immobilization

Abstract

Dielectrophoresis (DEP) is a nondestructive and noninvasive method which is favorable for point-of-care medical diagnostic tests. This technique exhibits prominent relevance in a wide range of medical applications wherein the miniaturized platform for manipulation (immobilization, separation or rotation), and detection of biological particles (cells or molecules) can be conducted. DEP can be performed using advanced planar technologies, such as complementary metal-oxide-semiconductor (CMOS) through interdigitated capacitive biosensors. The dielectrophoretically immobilization of micron and submicron size particles using interdigitated electrode (IDE) arrays is studied by finite element simulations. The CMOS compatible IDEs have been placed into the silicon microfluidic channel. A rigorous study of the DEP force actuation, the IDE's geometrical structure, and the fluid dynamics are crucial for enabling the complete platform for CMOS integrated microfluidics and detection of micron and submicron-sized particle ranges. The design of the IDEs is performed by robust finite element analyses to avoid time-consuming and costly fabrication processes. To analyze the preliminary microfluidic test vehicle, simulations were first performed with non-biological particles. To produce DEP force, an AC field in the range of 1 to 5 V (peak-to-peak) is applied to the IDE. The impact of the effective external and internal properties, such as actuating DEP frequency and voltage, fluid flow velocity, and IDE's geometrical parameters are investigated. The IDE based system will be used to immobilize and sense particles simultaneously while flowing through the microfluidic channel. The sensed particles will be detected using the capacitive sensing feature of the biosensor. The sensing and detecting of the particles are not in the scope of this paper and will be described in details elsewhere. However, to provide a complete overview of this system, the working principles of the sensor, the readout detection circuit, and the integration process of the silicon microfluidic channel are briefly discussed.

Keywords: CMOS biosensor; biomolecules; dielectrophoretic immobilization; lab-on-chip; microfluidic.

Figure 1

Multi-fingered planar interdigitated electrodes (IDEs).

Figure 2

(a) E-Field distribution above two adjacent fingers of IDE; (b) Electric field magnitude as a function of distance above IDEs.

Figure 3

Interdigitated electrode: (a) Electric field distribution of the IDE; (b) Equivalent capacitive contributions from IDE and material-under-test (MUT).

Figure 4

(a) High frequency 60 GHz integrated homodyne reflectometer; (b) The Gilbert-cell mixer; (c) Sample transfer function characteristics of the mixer.

Figure 4

(a) High frequency 60 GHz integrated homodyne reflectometer; (b) The Gilbert-cell mixer; (c) Sample transfer function characteristics of the mixer.

Figure 5

(a) Processed IDEs (sensors) structures b; (b) Complementary metal-oxide-semiconductor (CMOS) integrated microfluidic lab-on-a-chip device with size of 5 × 5 mm².

Figure 6

Packaging process of microfluidic lab-on-a-chip: (a) CMOS fabrication; (b) Channel formation; (c) Bonding process by a three-wafer-stack approach [28].

Figure 7

(a) 3D-geometry and; (b) 2D-geometry of the model device used to study the dielectrophoretic forces on particle tracing.

Figure 8

Simulation analysis steps for 3.5 µm diameter size particles: (a) Electric potential distribution in the microfluidic channel at Ʋ = 5 V at a fixed frequency of 10 MHz; (b) Electric field distribution contour plot in the microfluidic channel; (c) Velocity field across the microfluidic channel; (d) Particle trajectories with respect to the applied electric potential and the force acting on the particles leading to the immobilization of the particles at the surface of electrodes.

Figure 9

Clausius Mosotti (CM) factor for 10 µm diameter-sized particle as a function of frequency.

Figure 10

Impact of voltage variation on the DEP force for particles at constant fluid flow velocity (50 µm/s), geometrical parameters of IDEs (electrode width of, 30 µm, and spacing of, 20 µm) and DEP operating frequency (1 MHz). (a) Diameter size of 3.5 µm; (b) 0.5 µm.

Figure 11

Influence of fluid flow velocity on tracing of the 0.5 µm particles through the microfluidic channel at a constant voltage of 5 V and operating frequency of 1 MHz. At flow rates of: (a) 50 µm/s; and (b) 30 µm/s.

Figure 12

Finite element modeling (FEM) results for the immobilization probability with different ratios of the IDE’s spacing and width ($\frac{S}{W}$) for 10 and 3.5 µm-sized particles at 1 MHz and fluid velocity of 50 µm/s: (a) 10 µm; (b) 3.5 µm particle.

Figure 13

Impact of IDE’s width in symmetric structures ($S=W)$ on immobilization probability of 10 and 3.5 µm particles under the same voltage and fluid velocity.

Figure 14

Impact of IDE’s geometrical parameters on immobilization probability (IP) of particles with diameters of 10 and 3.5 µm, keeping voltages and fluid velocities constant: (a,b) illustrate IP variations with respect to different widths at fixed spacings of 5 and 20 µm, respectively; (c,d) show the impact of spacing size on IP at fixed widths of 5 and 45 µm, respectively.

Figure 15

Impact of the optimized parameters (geometrical parameters and fluid flow velocity) on immobilization of submicron particles (0.5) µm at constant voltages of 5 V and fluid flow velocity of 30 µm/s.

Figure 16

IDE’s capacitance vs. water dielectric permittivity [30] at 1MHz excitation frequency, observed from room temperature up to 50 °C.