Capitulo I: Marco Teórico Referencial
1.5. Industria del Software en Cuba
Microfluidic devices fall into three distinct categories that are distinguished by the combination of phases of fluid within the microfluidic channels. Continuous flow systems are single liquid phase, whereas droplet systems consist of two or more mutually immiscible phases. By contrast, digital devices do not possess channels in the traditional sense instead moving droplets of fluid between electrodes by means of dieletric forces. The following sections describe each of these types in more detail. Table 3.1 compares the relative utility of each of these types.
3.2.1. Continuous
Continuous flow microfluidics involves devices with channels made in suitable materials (see section 3.7) that have a single liquid phase flowing through them. A variety of methods can be used to control the flow of fluid through channels including on chip valves and pumps, off chip pumps, semi-permeable membranes, magnetic fields and electro-osmotic pumps (EOPs) (see section 3.12). Due to surface wetting effects, single phase devices are prone to contamination between reagents and must undergo washing or surface treatment to avoid these issues. Continuous flow devices are generally easier to fabricate and most widely applicable. Each of these mechanisms will be discussed during this introduction.
71 3.2.2. Droplet
Droplet microfluidics involves the formation of droplets of one phase, such as an oil phase in another phase, such as an aqueous phase. The hydrophobic oil does not mix with the water-based polar fluid and so droplets of one can be carried by a flow of the other. Droplets are kept separate from each other and do not contact the internal surfaces of the device, provided the device material and droplet fluid properties are appropriate. Droplet microfluidics makes use of the same flow control methods as continuous flow devices (see sections 3.11 and 3.14), but also makes use of the geometry of channels to control the mixing and merging of droplets (see section 3.16). Droplet microfluidic devices require accurate and consistent control of flow rates and often require stabilisation prior to running productively. Furthermore, the liquids may contain toxic oils or surfactants.
3.2.3. Digital
Digital microfluidics involves the movement of droplets of a polar phase across electrically active surfaces in air or non-polar/conducting medium by electrowetting7,8. Digital microfluidics is often referred to as electrowetting on dielectric (EWOD) microfluidics. Confusingly, because digital microfluidics employs the movement of droplets, digital microfluidics is sometimes referred to as droplet microfluidics. Digital microfluidic platforms can be prepared by patterning electrodes across parallel glass plates using a pattern mask. As a result EWOD does not require mould production or photolithography and so can be produced relatively easily. The required devices are complicated, however, and as droplets transit around the surface of the device, they may leave residue that can cause contamination of subsequent droplets. Furthermore, the range of suitable fluids is limited by the requirements of the method. Surface acoustic waves (SAWs) and ultrasound can be employed to produce and manoeuvre droplets.
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Type
Risk of
contamination
Ease of use
Sample
volume
Flexibility
Continous
Moderate High Moderate LowDroplet
Low Moderate Low ModerateDigital
High Moderate Low HighTable 3.1: Comparison of the relative utility of the three primary types of microfluidic device.
3.3. Microfabrication methods
At the heart of microfluidic devices is the production or microfabrication process. Techniques such as lithography, used to mass produce ICs, can be used to etch channels directly into materials such as glass or silicon that are relatively impervious to attack by organic solvents or aqueous solutions of neutral pH. Lithography is also frequently used to pattern spun layers of photoresist (usually SU-8). Micromachining is employed to create channels directly in softer materials, such as plastic. Patterns made in a master can then be reproduced in a secondary material, such as PDMS or poly(methyl methacrylate) (PMMA), through a process called lithography, electroplating and moulding (LIGA). In both the lithographic and micromachining cases, the channels are formed initially as grooves on a surface, the fourth wall of which is formed when the patterned surface is sealed against another, flat surface.
3.4. Photolithographic techniques
Photolithography allows the patterned etching or deposition of materials onto an underlying material. Typically, a layer of photoresist is applied to a surface, which is then patterned using a photomask in conjunction with exposure to light (usually UV, depending
73 on the photoresist). Photomasks can be produced be a range of techniques depending on the requirements of the application: Low resolution (>150 nm) masks can be prepared by printing onto a transparent medium and higher resolution masks generally require the employment of phase-shifting, he use of short wavelength light such as x-rays or immersion lithography. Once patterned photoresist is then developed, where the excess resist is removed leaving behind a patterned layer of photoresist. Although this photoresist can be used directly as part of a microfluidic device, it is more common to etch the underlying material using an etchant to which the photoresist is resistant. After this process, remaining photoresist can be removed leaving the negative of the photoresist pattern engraved into the underlying material.
Photolithographic techniques are capable of producing features and channels 100’s of nm in size. The scale of features typically used in microfluidic devices (1-10 µm) are easily produced by photolithography. Furthermore, photomasks can be reused and patterns repeated for mass-manufacturing. Silicon is the most commonly used material in photolithography, but other materials can also be etched such as HF etching of glass. Accurate production of small devices with small feature sizes (<10 µm) by photolithography requires precisely manufactured photomasks, expensive equipment such as mask aligners and the use of toxic or caustic chemicals. This requires lithographic techniques be performed by experienced personal operating in a controlled laboratory environment. In addition to constituting the devices themselves, photolithographically patterned devices can be used as moulds to produce microfluidic devices by casting or hot embossing using suitable polymers such as PDMS and polymethylmethacrylate (PMMA).
3.5. Micromachining
Micromachining uses small drill bits or a laser to pattern a surface by directly removing material from the surface. Parts can be designed in 3D CAD software and produced using
74 CNC machines. Micromachining is best employed with hard materials such as PMMA, that will not deform during the milling process compared to softer materials, such as PDMS. Although variations in parts can be introduced as drill bits undergo wear, the cost of replacing drill bits is insignificant next to the cost of the CNC machine itself or the cost of an equivalent lithographic setup. Lasers, which do not undergo wear, but whose power may fluctuate, can be used to machine both hard and soft materials but may leave rough or damaged surfaces9. The primary limitation of micromachining is resolution; typical drill bit diameters are >100 µm which limits the minimum feature size. The primary benefit of micromachining is that parts can be produced rapidly without the need for toxic chemicals.