MÓDULO DE PRÁCTICAS PROFESIONALES NO LABORALES DE MAQUILLAJE INTEGRAL

Microfluidics is the science studying the behavior of extremely small amounts of fluids with volumes from tens of nanolitres down to picolitres flowing inside confined geometries with a characteristic length of the order of tens of micrometres or less.

The first microfluidic technology was developed in the early 1950s when efforts to dispense small amounts of liquids in the nanolitre and picolitre range were made [56], providing the basis for today’s inkjet technology [57]. A deeper interest on small amounts of fluids driven along tiny structures rose up in the 1980s when researchers tried to apply microma- chining technology inherited from silicon microelectronics to the realization of microfluidic channels. After capillarity force was used for the realization of the first miniaturized gas chromatograph (GC) by Terry et al. on a silicon wafer [58], other devices were obtained exploiting the advantages of microfluidics and efforts were spent to realize several micro- fluidic structures, such as microvalves and micropumps [59, 60].

Nevertheless the actual boom of microfluidics started in the 2000s, when polymeric ma- terials allowed to realize very easily prototypes of microfluidic devices at a reasonable cost [61, 62].

In the last years a renewed interest in more expensive materials such as silicon or glass is growing due to the need of devices able to avoid swelling, nonspecific bioadhesion and degradation problems of polymer based chips and to support both microfluidic stages and optical or electronical ones [63, 64].

Since its birth microfluidics has been employed in a plenty of applications ranging from chemical synthesis to information technology, from biological analysis to drug delivery. The reason for such a success relies on the fact that microfluidics provides an extremely steady

36 3.1 The new age of Microfluidics

control on the manipulated samples and a very low reagents consumption. Nevertheless it allows high throughput and parallelization reachable increasing the complexity of the devices without a significant increase in the device overall size.

The very small size of the channels in the usual range of flow rates employed lead to low Reynolds number1 _{(Re < 100) and then to laminar flow as well as typically large values}

of Peclet number2 _{(measuring the ratio of the convective to diffusive transport): this is}

the key-path to get high control both in space and time over the transport of chemical or biological spiecies [65–67].

These are the main bricks at the basis of Lab-on-Chip (LOC) technology, the more prom- ising field of microfluidics which has the aim to transfer all laboratory operations into small portable microfluidic devices.

The microfluidic channels of these devices are usually made of polymeric materials such as PDMS or PMMA and obtained by moulding on masters realized by photolitographic techniques [61, 62]; less often they can be realized by chemical etching, laser ablation, mi- cromachining (or a combination of these techniques) on stiffer materials such as silicon or glass. Polymers are preferred since they are easier to shape and they are almost in- expensive. On the other hand silicon and glass, although more expensive, can offer more stable chips at high pressure conditions and above all they are more and more durable since they don’t suffer deterioration like polymer materials. The employment of new materials for microfluidcs seems to be a challenge for recent research and many efforts have been spent espescially towards the applicability in biology and medicine and to the integration of multiple stages able to perform multiplexed analysis on liquid samples. In particular many micro-devices have been already realized, able to pull the fluids inside the channels, to manipulate small amounts of liquids, to mix and merge them, to catch and sort particles dispersed in the fluids, to perform analyses of diluted species and many others, but it is still a challenge the integration of all these stages in order to realize a single multi-purpose micro-device which gets rid of all external macro add-ons needed to make up for the lack of micro-technology solutions. In fact what is hardly highlighted in microfluidics applica- tions is that although a plenty of micro-devices manipulating nanolitres droplets have been

1_{Re =} ρuL

µ , where ρ is the density of the fluid, u is its mean velocity, L is the characteristic linear dimension of the flow and µ is the fluid dynamic viscosity.

2_{Pe =} Lu

D , where L is the characteristic linear dimension of the flow, u is the mean velocity and D the mass diffusion coefficient of involved species.

3.1 The new age of Microfluidics 37

realized, they usually need macro syringe pumps or pressure controllers to operate, or even there exist awsome devices treating biological samples but finally the analysis is carried out putting the chip under the objective of a "big" microscope.

In this thesis the very first attempt of realizing a fully integrated opto-microflduic plat- form on lithium niobate is presented and the complete integration on the same material of a microfluidic stage with an optical stage for droplet analysis is shown. This is a first step towards the integration of all desirable stages in a single micro-device since lithium niobate has been already showed to be suitable for the realization of pumping micro- systems [21, 68, 69], fluid manipulation devices [70, 71] and optical circuits [72] and in addition it is biocompatible [73].

3.1.1 Droplet Microfluidcs

At the early birth of microfluidics the perspected possibility to perform typical laboratory operations inside a microfluidic chip came up against the peculiarities of fluid flow inside microchannels.

The Reynolds number of such devices is typically very low, always below 100, due to typical fluid velocity that usually doesn’t exceed the order of 1m/s and characteristic dimension of microfluidic channels normally ranging from 10µm to 300µm. The typical regime of microfluidics experiments is the laminar flow and this actually makes molecular diffusion the only way for mixing different fluids. This process is quite slow across typical distances of a microfluidic channel and so performing fast reactions inside a microfluidic chip is not achievable.

Moreover laminar flow together with the particular boundary conditions due to the con- straint of zero fluid velocity at the solid walls of the channels leads to parabolic velocity profiles. The resulting velocity gradient along the direction perpendicular to the flow gives rise to axial dispersion of the injected liquid compounds and so to poor control on the concentrations of flowing reagents.

These difficulties started to be overcome at the beginning of this century thanks to the advent of droplet based microfluidics. The main idea is to confine the fluid of interest (containing chemical reagents, molecules or biological samples) inside droplets surrounded by another immiscible fluid phase used to carry droplets along the microfluidic channels. The fluid that makes up the droplets is generally called dispersed phase while the outer