Design and Development of a Traveling Wave Ferro-Microfluidic Device and System Rig for Potential Magnetophoretic Cell Separation and Sorting in a Water-Based Ferrofluid

Abstract

The timely detection and diagnosis of diseases and accurate monitoring of specific genetic conditions require rapid and accurate separation, sorting, and direction of target cell types toward a sensor device surface. In that regard, cellular manipulation, separation, and sorting are progressively finding application potential within various bioassay applications such as medical disease diagnosis, pathogen detection, and medical testing. The aim of this paper is to present the design and development of a simple traveling wave ferro-microfluidic device and system rig purposed for the potential manipulation and magnetophoretic separation of cells in water-based ferrofluids. This paper details in full: (1) a method for tailoring cobalt ferrite nanoparticles for specific diameter size ranges (10-20 nm), (2) the development of a ferro-microfluidic device for potentially separating cells and magnetic nanoparticles, (3) the development of a water-based ferrofluid with magnetic nanoparticles and non-magnetic microparticles, and (4) the design and development of a system rig for producing the electric field within the ferro-microfluidic channel device for magnetizing and manipulating nonmagnetic particles in the ferro-microfluidic channel. The results reported in this work demonstrate a proof of concept for magnetophoretic manipulation and separation of magnetic and non-magnetic particles in a simple ferro-microfluidic device. This work is a design and proof-of-concept study. The design reported in this model is an improvement over existing magnetic excitation microfluidic system designs in that heat is efficiently removed from the circuit board to allow a range of input currents and frequencies to manipulate non-magnetic particles. Although this work did not analyze the separation of cells from magnetic particles, the results demonstrate that non-magnetic (surrogates for cellular materials) and magnetic entities can be separated and, in some cases, continuously pushed through the channel based on amperage, size, frequency, and electrode spacing. The results reported in this work establish that the developed ferro-microfluidic device may potentially be used as an effective platform for microparticle and cellular manipulation and sorting.

Keywords: cellular; circuit board; design; diagnosis; diseases; ferro-microfluidic; ferrofluid; frequency; heat; magnetic; manipulation; medical; non-magnetic; separation; traveling wave.

Figure 1

Overview of the programmable chip platform and current waveform: (a) Photo of the first fabricated programmable electronic chip base. The arrows going in represent the current amplitudes supplied to the chip at a 90° phase, and the arrows coming from the chip represent the output currents at a 90° phase difference. (b) The current sinusoidal input current waveforms for I₁ and I₂.

Figure 2

Schematic diagram of the experimental rig electronic components.

Figure 3

Photograph of the experimental rig setup: (a) microscope and cooling system setup with the oscilloscope and (b) the 3D-printed resistor housing and cooling setup.

Figure 4

Computational model of the electronic chip and copper base for the heat dissipation analysis: (a) CAD model, (b) meshed model, and (c) close view of electrode meshing.

Figure 5

System rig and water-cooled heat dissipation setup: (a) full system with the ferro-microfluidic device and water block and (b) the thermal image of the electrodes with an input current.

Figure 6

Thermal experiment setup.

Figure 7

Thermal simulations at 2 W for 3 s: (a) thermal contours and (b) thermal iso-contours. The dashed lines in the iso-contour represent the area where the ferro-microfluidic device will sit. The black arrow on the color scale represents the temperature threshold for cell damage.

Figure 8

Temperature vs. time probe profile plot at the first electrode for 7 A without a heat sink and proper cooling.

Figure 9

Temperature vs. time profile of the electrodes at various current settings. The dashed line represents the thermal breakdown region for the copper electrodes.

Figure 10

Photograph of the damaged chip during the forced convection setup.

Figure 11

Averaged steady-state temperature for each current setting. Ambient air cooling is without a cooling device. Cooling method 1 is using a micro-cooler setup with water at 0 °C, cooling method 2 is using a Neslab bath circulator setup with the temperature set to 6 °C, and cooling method 3 is using a Neslab bath circulator setup with the temperature set to 0 °C.

Figure 12

Individual particle sizes as extracted from TEM images for the first batch: (a) TEM image of the particles and (b) the log-normal distribution with a 48.53 nm average particle diameter.

Figure 13

X-ray diffraction results for the 1st sample of cobalt ferrite particle tailoring.

Figure 14

Histogram of particle sizes for the second batch with an average diameter of 17.9 nm.

Figure 15

Microscope image of cobalt ferrite particles suspended in water in the PDMS single microchannel device. The numbered regions show the locations of the largest particle aggregations. The blurry particles represent particles closer to the bottom of the channel.

Figure 16

SEM images of 1 µm fluorescent microspheres.

Figure 17

Particle image processing results in PIVlab for 4 µm diameter particles: (a) raw image and (b) PIVLAB pre-processed image with filters prior to cross-correlation analysis.

Figure 18

Overview of the particle image processing methodology in PIVlab. (a) Top view of 4 µm diameter particles moving in the micro-channel under excitation, and (b) The processed velocity contour image. The electrode (gold) and spacing (green) are shown below the figures.

Figure 19

Top view of the microfluidic channel with the ferrofluid: (a) Image of 10 µm and 1 µm diameter microspheres randomly dispersed in the channel and (b) After the excitation, particles collect in the interelectrode spacing. The electrode (gold) and spacing (green) are shown below the figures.

Figure 20

Velocity contour of 10 particles moving between the electrodes at 10 Hz and with a large electrode spacing. The electrode (gold) and spacing (green) are shown below the figure.

Figure 21

Plot of the velocity distribution in the middle of the channel and across the electrode region.

Figure 22

Histogram of the velocity distribution from the image dataset.

Figure 23

Velocity contour of 1 µm diameter particles under 750 mA and 10 Hz.

Figure 24

Velocity contour of 10 µm diameter fluorescent particles at 4 A and 10 Hz.

Figure 25

Vorticity contours of 10 µm diameter fluorescent particles at 4 A and 10 Hz.

Figure 26

Velocity distribution extraction from the centerline of the 10 µm diameter particle study at 4 A and 10 Hz.

Figure 27

Velocity profile extraction from the middle of the first electrode for the 10 µm diameter particle study at 4 A and 10 Hz.

Figure 28

Particle images and contours obtained at 6 A and 10 Hz before and during excitation: (a) image of particles randomly dispersed before the field is turned on, (b) particle images obtained during excitation, and (c) the processed velocity contour of 1 um diameter fluorescent particles at 6 A and 10 Hz.