The centrifugal micro-fluidic biochip or centrifugal micro-fluidic biodisk is a type of lab-on-a-chip technology, also known as lab-on-a-disc, that can be used to integrate processes such as separating, mixing, reaction and detecting molecules of nano-size in a single piece of platform, including a compact disk or DVD. This type of micro-fluidic biochip is based upon the principle of microfluidics to take advantage of non-inertial pumping; for lab-on-a-chip devices using non-inertial valves and switches under centrifugal force and Coriolis effect, this is in order to distribute fluids about the disks in a highly parallel order.

This biodisk is an integration of multiple technologies in different areas. The designer must be familiar with the process of biology testing before designing the complex micro-structures in the compact disk. Some basic components such as valves, mixing units, and separating units should all be used to complete the full testing process. The basic principles applied in such micro-fluidic structures are centrifugal force, Coriolis effect, and surface tension. The micromachining techniques, including patterning, photolithography, and etching should all be used as long as the design is verified. Once the testing process is successful in the biodisk, the detection technique is started. There are many methods proposed by scientists in this area. The most popular method is immunoassay which is widely used in the testing of biology. The final step is receiving data from the biodisk by means of a CD drive and modifying either software or hardware that can achieve this function. An example method is reading data from the biodisk using a common CD drive with dedicated software, which has the advantage of being low on cost.

Once the centrifugal micro-fluidic biochip is developed well enough to be manufactured on a large scale, it is theorized to cause a wide effect on the industry as well as medical care, especially in developing countries, where high-precision equipment is not available. People in developed countries who are willing to do such regular home-care detections can also benefit from this technology.

History The centrifugal microfluidic platform, including the chip and the device, has been a focus of academic and industrial research efforts for almost 40 years. Primarily targeting biomedical applications, a range of assays have been adapted on the system. The platform has found success as a research or clinical tool and has been further commercialized recently, notably at Gamera Bioscience led by Alec Mian, Greg Kellogg, and Stephen Higgins, who implemented the concept using a compact disc format in1995. Nonetheless, this micro-fluidic lab-on-a-chip technology has experienced a rapid surge over the last 10–15 years, and new developments in centrifugal microfluidic technologies have the potential to establish widespread utilization of the platform. Therefore, different liquid-handling platforms have been developed to implement unit operations such as sample take-up, sample preconditioning, reagent supply, metering, aliquoting, valving, routing, mixing, incubation, washing, as well as analytical or preparative separations. The integration of such sample preparation, incubation, analysis on a self-contained disc in a device that controls the spinning for automatic performance encourages the sample-to-answer diagnosis in the point-of-care biomedical platform.

Dr. Marc Madou in UC Irvine is one of the leaders in the centrifugal micro-fluidic biochip. He has done several research projects on this area and has made success such as pneumatic pumping in centrifugal microfluidic platforms, integration of 3D carbon-electrode dielectrophoresis, and serial siphon valving. His group members are working on projects including cell lysis, PCR card, DNA hybridization, anthrax diagnostics and respiratory virus detection (see external links). Dr. Hua-Zhong Yu in SFU.ca also made great progress in this area, proposing a new digitized molecular diagnostic reading method and a new DNA detection method on plastic CD. (see external links) Dr. Gang Logan Liu in UIUC is currently also focusing on this area (see external links).

Structure design

The design of structure bases on the principle of microfluidics and typical components are used in the platform. many structures for centrifugal microfluidic biochips have been developed, with more interesting ones yet to be released. Madou's group invented the valve-chamber structure in 2004. In recent years, Saki Kondo released the vertical liquid transportation structure, which pushed the design to become a three-dimensional concept. Madou's group also invented a serial siphon valving structure which makes flow control much easier. Hong Chen created a spiral microchannel which allows parallel testing with more steps.

Principle

The principle for the centrifugal micro-fluidic biochip includes the basic forces of a particle as well as the principle of flow control.

For a particle in the flow the basic forces are centrifugal force, Coriolis force, Euler force and viscous force.

The centrifugal force plays a role as a pump in the fluid flowing. It offers the basic source to transfer the fluid flowing from the inner radius of CD to the outer radius. The magnitude of the centrifugal force is determined by the radius of particle location and the rotational speed. The formula for centrifugal force density is:

where N is the mass density of the liquid, ω the angular frequency and r the (radial) distance between the particle and center of the disk.

The formula for Coriolis force density is:

where u is the flow velocity.

The Coriolis force generates when the liquid has a velocity component along the radial direction. This force is generally smaller than the centrifugal force when the rotating speed is not high enough. When it comes to a high angular frequency, the Coriolis force makes a difference to the flow of liquid, which is often used to separate fluid flow in the separation unit.

Another basic force is Euler force, which is often defined as the acceleration of angular frequency. For example, when the CD is rotating at a constant speed, the Euler force is relatively slow. The formula for Euler force density is:

As for a particle in the fluidic flow, the viscous force is:

v is the viscosity of the liquid.

As for the entire fluid flow, surface tension plays an important role in flow control. When the flow comes across a varied cross section, the surface tension will balance the centrifugal force and as a result block the flow of liquid. Higher rotation speed is necessary if the liquid would like to enter the next chamber. In this way, due to surface tension, the flowing process is divided into several steps which makes it simpler to realize flow control.

Typical component

There are various typical units in a centrifugal microfluidic structure, including valves, volume metering, mixing and flow switching. These types of units can make up structures that can be used in a variety of ways.

Valves The principle of valves is the balance between centrifugal force and surface tension. When the centrifugal force is smaller than the surface tension, the liquid flow will be held in the original chamber; when the centrifugal force overbalances the surface tension due to a higher rotating speed, the liquid flow will break the valve and flow into the next chamber. This can be used to control the flow process simply by controlling the rotating speed of the disk.

The most commonly used valves include the hydrophilic valve, the hydrophobic valve, the syphon valve and sacrificial valve.

As for hydrophilic and hydrophobic valves, the generation of surface tension is almost the same. It is the sudden change of cross section of the channel that generates the surface tension. The liquid flow will be held in a hydrophilic channel when the cross section suddenly becomes large, while the flow will be held when the cross section of hydrophobic channel suddenly shrinks.

The siphon valve is based on the siphon phenomenon. When the cross-section of the channel is small enough, the liquid in the chamber can flow along the channel due to surface tension. Unlike hydrophilic or hydrophobic valves, surface tension acts as a pump in this model while centrifugal force acts as resistance.

The sacrificial valve is a technique that is controlled by laser irradiation. These sacrificial valves are composed of iron oxide nanoparticles dispersed in paraffin wax. Upon excitation with a laser diode, iron oxide nanoparticles within the wax act as integrated nanoscale heating elements, causing the wax to quickly melt at relatively low intensities of laser diode excitation. The valve operation is independent of the spin speed or the location of the valves and therefore allows for more complex biological assays integrated on the disk.

Volume metering

Volume metering is a typical function of centrifugal fluidics to reach a certain amount of liquid reagent. It can be achieved by simply connecting an overflow channel to the chamber. Once the liquid is at the level of the overflow channel, the rest of the liquid will be routed into the waste chamber connected to the overflow channel.

Mixing

Mixing is an important function in microfluidics, which combines various reagents for downstream analysis. As the fluid is confined in the micro-scale domain, mixing becomes difficult due to the low Reynolds number with laminar flow. That indicates that there is no convective mixing but diffusion, which limits the mixing process. This problem can be solved using several methods. A typical way is to rotate the disk in different directions, namely clockwise and anticlockwise rotation.

Flow switching

Flow switching is necessary when routing reagents into different chambers. A common method for flow switching in a centrifugal device is to utilize the Coriolis force within a Y-shaped structure. When the rotating speed is too low, the liquid flow will follow the original path; when the rotating speed is high enough, which is at almost the same level as centrifugal force, the liquid flow will be routed into another chamber.

Others

Other functions such as sedimentation are also used in microfluidic platforms when necessary. Due to the different mass and radius between different particles, these particles can be separated by viscosity and velocity. In this way, the sedimentation of different particles can be achieved.

Materials

Many structures can be formed using the most common, rapid prototyping technology, soft lithography with polydimethylsiloxane(PDMS). PDMS is an inexpensive, clear elastomeric polymer with rubbery mechanical properties at room temperature. In the laboratory, PDMS is mixed in small batches, poured onto moulds, for example, poly(methyl methacrylate) (PMMA), with micro-scale features, and cured at moderate temperatures for minutes to hours. Open PDMS channels are closed by adhering the channel bearing component to a glass slide or a second, flat piece of PDMS. Inlets and outlets can be formed easily using punch tools. Although many surface modifications are not permanent on PDMS due to its relatively high chain mobility compared with polymers, PDMS still remains relevant as a material for microfluidic applications.