Labs-On-A Chip
Microfluidics are tiny liquid handling devices with channels up to 500 microns wide. The channels transport, mix, or dispense fluid samples, analytes, and reagents. But liquids don't flow through the small channels easily and must be coaxed by several methods. Designers of the devices are getting insights and assistance for doing so from CFD software. Many recent tiny devices include lab-on-a-chip (LOC) ideas that might, for example, take in micro-drops of blood and generate diagnostic readouts.
Micro fluidics
The advantages of LOCs are that they require samples in small volumes, they reduce analysis times compared to central or hospital labs, and the tests are readily automated. Conducting tests at bedsides also reduces handling errors, mix-ups between patients, and things that get lost. Also, bedside tests quickly provide information to guide diagnoses and treatment. In addition, several tests can run simultaneously. Material costs are low because the devices are mostly glass, silicon, and plastic and their manufacturing technology, once geared up, can produces millions at a time, just like ICs.
But creating just a few physical prototypes of such “labs” is expensive. So designers simulate the physical phenomena in CFD software to optimize flows. “CFD is gaining wider use as a tool in all sectors of the health care industry especially in device design optimization and pharmaceuticals,” says senior consulting engineer Marc Horner with Fluent Inc., Evanston, Ill. (fluent.com)
“Although moving microliters is just a bit more complex than working with several milliliters of the same stuff, there are several ways to move and mix small amounts,” says Horner. “Techniques include electrophoresis, which separates molecules based on charge, and electro-osmosis, which transports fluid by the net motion of ions along a charged surface. This latter method generates flow in channels by getting ions to stream along the wall. That drags the rest of the fluid with it.”
Electrohydynamics, a more frequently used technique, applies a voltage drop across a channel. “A charged liquid then moves through the system in a reaction to the field,” says Horner. Isotachophoresis uses two different buffer systems to create zones into which analytes separate. Piezoelectric pumping uses piezoelectric membranes or diaphragms to move microliters.
Electrowetting also moves small samples. An electric field modifies the wetting behavior of a droplet in contact with an insulated electrode. It works on open surfaces but is more efficient in a sandwich. Imagine two plates just microns apart and with many small squares like a checkerboard on the facing surfaces, each addressed with a voltage. “Put a drop in the sandwich between two plates and turning squares on and off drives the drop around the plate,” says Horner. Electrowetting arrays can independently move a large numbers of droplets without pumps, valves, or fixed channels.
The gated valve, a dispensing technique, uses channels intersecting at right angles. With proper voltage, a sample is driven from the west leg across and down the south leg. If the voltage in the north leg drops momentarily, a little sample pops off into the east leg. Its volume is a function of the change in voltage on the north leg. The question researchers want to answer is how much sample comes off with the different voltage levels.
Multiphysics in a micro world
Enhancing biosensors to quickly detect biological molecules is a goal of U. of California professor Carl Meinhart. He's leading a research team that designs microfluidic devices. One of his team's microchannel device stirs samples of low-concentration analyte (the stuff to be analyzed) using electric fields.
Meinhart's team has developed a way to improve flow near the reaction surface to increase the transport of analyte using ac generated electric fields. Two electrodes are placed on a channel wall opposite a binding surface. An ac voltage generates fields and a swirling pattern in the fluid that transports a higher concentration of analyte towards the binding surface, thereby increasing the reaction rate. “Electrodes designed for this and an optimal driving voltage lets us reduce the detection time from ten hours to potentially just one,” says Meinhart.
To simulate stirring the fluid involves at least three different phenomena. For instance, a dielectrophoresis force is generated by a molecule acting as an electric dipole that reacts to an applied voltage. The field also nonuniformly heats the fluid. Electrical conductivity and permittivity are functions of temperature, so gradients in these parameters from the heating give rise to Coulomb and dielectric forces, which act as an electrothermal force that changes the fluid's motion. A third force comes from electro-osmosis. The fluid is a conductor, so the field triggers ions in the fluid to counterbalance the potential. The result is a thin layer of ions only a few nanometers thick at the electrodes surface. The electric field leaves at a direction normal to the electrode surface, but if the ion layer is only tens of nanometers thick, the field has a slight tangential component, and this electro-osmotic force contributes to fluid motion.
The team combines experimental results with numerical simulations to test various theories. Creating the numerical model involves several physical phenomena such as electrical potentials, electric fields, temperature, electrical conductivity and permittivity, fluid velocity, and analyte concentration. The team solved the model in Comsol analysis software from Comsol Inc., Burlington, Mass., (comsol.com). Meinhart simultaneously coupled six equations in the software to:
Solve the base electrostatics problem using Laplace's equation.
Solve the thermal-energy equation with Joule heating (heat dissipated by an electrical current through a resistor) from the electric field as a source term.
Calculate the nonlinear electrothermal force using results from electrostatics and temperature simulations.
Solve the fluid-velocity field in the channel using Navier-Stokes equations with the electrothermal force added as a source term. From the electrothermal force equation, the Coulomb force dominates at low frequencies and the dielectric force dominates at high frequencies.
Use a time-dependent diffusion-convection equation to predict the analyte's suspended concentration within the microchannel.
Solve the 1D heterogeneous reaction equation and couple the 1D binding surface to the 2D microchannel.
Incoming flow in the model has a small concentration of the biological analyte, moving flows from left to right in the accompanying diagram. Without voltage to the two electrodes on the bottom, the flow profile looks like the classic parabola with zero velocity at the walls and maximum flow in the center. The fluid moves the analyte which is then absorbed by the reaction surface on the upper boundary. Any remaining concentration exits the channel on the right side with the fluid. The model solves the steady-state flow interacting with the electric field and the resulting electrothermal force.
After applying an ac voltage, the flow profile is displaced towards the binding surface. This indicates the analyte concentration is pushed towards the binding surface faster in the presence of an electric field. A study revealed that 14 V rms applied to electrodes increases the binding rate in the first few minutes by a factor of almost five. “Optimizing electrode geometry and placement through simulations can make this technique useful for a variety of microfluidic immuno-sensors,” says Meinhart. The simulation model let the team examine effects of different geometries for the microchannel as well as different locations for the binding surface and electrodes.
| Fluid-handling technique | What it does |
| Electrophoresis | Separates flows based on charge |
| Electro osmosis | Coaxes a liquid through a capillary with an electric field across it. This generates flow in channels by getting ions to stream along the wall and drag the rest of the fluid with it. |
| Isotachophoresis | Uses two different buffer systems to create zones into which analytes separate |
| Piezoelectric pumping | Uses piezoelectric crystals to move microliters |
| Electrohydynamics | Applies a voltage drop across a channel. A charged species then moves through the system in a reaction to the field. |
| Electrowetting | An electric field modifies the wetting behavior of a droplet in contact between electrode plates and allows moving them around the plate. It also works less efficiently on open surfaces. |
Building a better blood pump
Not all CFD simulations are microscopic. For example, simulating a centrifugal blood pump let designers COBE Cardiovascular in the U.K. (cobecv.com) examine the pump's performance and identify potential problems for future redesigns.
Blood pumps can break down red bloodcells, or cause clotting on pump materials, or both. High-shear stresses and tortuous flow paths destroy the blood cells. And clotting stems from high-shear stress, turbulence, or contact with bioincompatible materials.
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