Advances in microfluidic materials, functions, integration, and applications.

Microfluidics consist of microfabricated structures for liquid handling, with cross-sections in the 1–500 μm range, and small volume capacity (fL-nL). Capillary tubes connected with fittings,1 although utilizing small volumes, are not considered microfluidics for the purposes of this paper since they are not microfabricated. Likewise, millifluidic systems, made by conventional machining tools, are excluded due to their larger feature sizes (>500 μm). Though micromachined systems for gas chromatography were introduced in the 1970’s,2 the field of microfluidics did not gain much traction until the 1990’s.3 Silicon and glass were the original materials used, but then the focus shifted to include polymer substrates, and in particular, polydimethylsiloxane (PDMS). Since then the field has grown to encompass a wide variety of materials and applications. The successful demonstration of electrophoresis and electroosmotic pumping in a microfluidic device provided a nonmechanical method for both fluid control and separation.4 Laser induced fluorescence (LIF) enabled sensitive detection of fluorophores or fluorescently labeled molecules. The expanded availability of low-cost printing allowed for cheaper and quicker mask fabrication for use in soft lithography.5 Commercial microfluidic systems are now available from Abbott, Agilent, Caliper, Dolomite, Micralyne, Microfluidic Chip Shop, Micrux Technologies and Waters, as a few prominent examples. For a more thorough description of the history of microfluidics, we refer the reader to a number of comprehensive, specialized reviews,3, 6–11 as well as a more general 2006 review.12 The field of microfluidics offers many advantages compared to carrying out processes through bulk solution chemistry, the first of which relates to a lesson taught to every first-year chemistry student. Simply stated, diffusion is slow! Thus, the smaller the distance required for interaction, the faster it will be. Smaller channel dimensions also lead to smaller sample volumes (fL-nL), which can reduce the amount of sample or reagents required for testing and analysis. Reduced dimensions can also lead to portable devices to enable on-site testing (provided the associated hardware is similarly portable). Finally, integration of multiple processes (like labeling, purification, separation and detection) in a microfluidic device can be highly enabling for many applications. Microelectromechanical systems (MEMS) contain integrated electrical and mechanical parts that create a sensor or system. Applications of MEMS are ubiquitous, including automobiles, phones, video games and medical and biological sensors.13 Micro-total analysis systems, also known as labs-on-a-chip, are the chemical analogue of MEMS, as integrated microfluidic devices that are capable of automating multiple processes relevant to laboratory sciences. For example, a typical lab-on-a-chip system might selectively purify a complex mixture (through filtering, antibody capture, etc.), then separate target components and detect them. Microfluidic devices consist of a core of common components. Areas defined by empty space, such as reservoirs (wells), chambers and microchannels, are central to microfluidic systems. Positive features, created by areas of solid material, add increased functionality to a chip and can consist of membranes, monoliths, pneumatic controls, beams and pillars. Given the ubiquitous nature of negative components, and microchannels in particular, we focus here on a few of their properties. Microfluidic channels have small overall volumes, laminar flow and a large surface-to-volume ratio. Dimensions of a typical separation channel in microchip electrophoresis (μCE) are: 50 μm width, 15 μm height and 5 cm length for a volume of 37.5 nL. Flow in these devices is normally nonturbulent due to low Reynolds numbers. For example, water flowing at 20°C in the above channel at 1 μL/min (2.22 cm/s) results in a Reynolds number of ~0.5, where <2000 is laminar flow. Since flow is nonturbulent, mixing is normally diffusion-limited. Small channel sizes also have a high surface-to-volume ratio, leading to different characteristics from what are commonly found in bulk volumes. The material surface can be used to manipulate fluid movement (such as by electroosmotic flow, EOF) and surface interactions. For a solution in contact with a charged surface, a double layer of charge is created as oppositely charged ions are attracted to the surface charges. This electrical double layer consists of an inner rigid or Stern Layer and an outer diffuse layer. An electrostatic potential known as the zeta potential is formed, with the magnitude of the potential decreasing as distance from the surface increases. The electrical double layer is the basis for EOF, wherein an applied voltage causes the loosely bound diffuse layer to move towards an electrode, dragging the bulk solution along. Charges on the exposed surface also exert a greater influence on the fluid in a channel as its size decreases. Larger surface-to-volume ratios are more prone to nonspecific adsorption and surface fouling. In particular, non-charged and hydrophobic microdevice surfaces can cause proteins in solution to denature and stick. We focus our review on advances in microfluidic systems since 2008. In doing this, we occasionally must cover foundational work in microfluidics that is considerably less recent. We do not focus on chemical synthesis applications of microfluidics although it is an expanding area, nor do we delve into lithography, device fabrication or production costs. Our specific emphasis herein is on four areas within microfluidics: properties and applications of commonly used materials, basic functions, integration, and selected applications. For each of these four topics we provide a concluding section on opportunities for future development, and at the end of this review, we offer general conclusions and prospective for future work in the field. Due to the considerable scope of the field of microfluidics, we limit our discussion to selected examples from each area, but cite in-depth reviews for the reader to turn to for further information about specific topics. We also refer the reader to recent comprehensive reviews on advances in lab-on-a-chip systems by Arora et al.10 and Kovarik et al.14