Digital microfluidics (DMF) is a powerful emerging technology which utilizes the precise manipulation of droplets in the microliter to nanoliter range to achieve complex laboratory analyses.
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DMF is often used in combination with other analytic tools like mass spectrometry, colorimetry, electrochemical analysis, and electrochemiluminescence.
Complex laboratory procedures can be achieved by combining and repeating several operations in a series of levels in a series of steps. The basic mechanism resembles that of more conventional protocols, but the volumes involved are much smaller, and the process is highly automated.
The production of microdroplets and their manipulation in this technology is governed by the three principles of electrowetting, dielectrophoresis, and immiscible-fluid flows.
Fundamental principles of DMF
DMF relies on the formation of droplets caused by the surface tension of a liquid. The more hydrophobic the surface, the less permeable it is by a liquid.
Hydrophobicity can generated using an electrical field, a process known as Electrowetting on Dielectric (EWOD). The application of this electric field creates polarized hydrophilicity of the surface of a liquid, which flattens droplets. The location of such polarization is controlled to produce a tension gradient that makes controlled droplet displacement to take place across the surface of the microfluidics platform.
The setup of a DMF platform is based on the substrates, electrodes and their configuration, the dielectric in use and its thickness, the hydrophobic layers, and applied voltage. Individual electrodes are patterned in an array on the bottom layer, while a continuous electrode is present on the top layer.
A dielectric material (such as glass) surrounds the bottom layer electrodes and is responsible for the accumulation of charge and electrical field gradients. The top layer is typically coated with a hydrophobic layer to create low surface energy at the point of contact of the microdroplet.
When a voltage is applied, the electrodes are activated, causing the surface droplet to become more or less wettable. If a nearby electrode is activated by a control voltage while the subjacent one is deactivated, the droplet will move. Thus the droplet can be manipulated along the line of electrodes by shifts in the electric potential along the linear array.
Recent advances in digital microfluidics
The 3D movement of droplets that is permitted by digital microfluidics allows two different tasks to be carried out simultaneously by the device. This has opened up biological applications extensively by making two environments accessible to the droplet. In addition, the chip size is reduced, and this gives greater liberty for platform design.
Another method called all-terrain droplet actuation can be useful for droplet transport over non-conventional surfaces such as curved, inverted, or non-horizontal shapes.
What are the advantages of digital microfluidics?
Digital microfluidics, also called lab-on-a-chip technology, has numerous advantages in life sciences research. These include its high potential for portability and its profound reduction in the amount of (often rare or costly) reagents or samples consumed.
Other important benefits include the high throughput capacity that digital micofluidic systems offer and the lack of power that it requires, due to its small size.
Applications of digital microfluidics
Digital microfluidic devices are typically used to separate and extract analytes of interest, using either magnetic particles, optical tweezers, liquid-liquid extraction, or hydrodynamic effects.
For instance, a droplet can be moved across an electrode array on the DMF device to a magnetic electrode where the magnetic particles are functionalized so that they can bind to the target analyte.
In the next step, the droplet is moved over the magnet and the field is eliminated to allow particle suspension in the droplet. The magnetic field is then brought back to immobilize the particles while the droplet is moved on. Repeating the process with wash and elution buffers yields the pure analyte.
This procedure has been carried out using anti-human serum albumin antibodies, demonstrating the potential of DMF in immunology.
Extraction of biological principles is often difficult because of small sample volumes used in DMF. However, the combination of DMF with macrofluidic systems can bypass this obstacle.
DMF has also been applied to create immunoassay devices, which greatly simplifies and extends the complicated procedure by automated delivery, mixing, incubation and washing of the analyte on the chip itself in the case of heterogeneous immunoassays. Some examples include the detection of human insulin, troponin I, TSH (thyroid-stimulating hormone) and 17-β estradiol.
Additionally, DMF can be coupled with mass spectrometry to reduce the use of solvent and reagent, while reducing the time needed for analysis.
Other fields of application include nuclear magnetic resonance spectroscopy, chemical synthesis in small-scale reactions to produce peptidomimetics or PET tracers, which are required in nanogram amounts. This speeds up the process and allows for automation while retaining 90-95% efficiency of the traditional large-scale syntheses.
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