current analytical techniques in biotechnology can potentially benefit from an integrated reduction in scale through lowered production and operating costs , and via the specific dynamics of flowing fluids occurring at the mico - scale , which enable the generation of accurate quantitative assays . microfluidics combines multiple disciplines including biotechnology , microtechnology , physics , and analytical chemistry and has flourished as a research field . the processes involved in biotechnology and microfluidics technologies take place on a very small scale ( microns to millimetres ) where some physical processes can become enhanced , e.g. osmotic movement , electrophoretic motility and surface interactions . microfluidics technology has essentially taken advantage of the inherent properties of liquids and gases at the microscale and combined this with semiconductor technology in order to build singular devices using a streamlined manufacturing process . in general , microfluidic devices can offer a number of advantages over more conventional systems , e.g. their compact size , disposable nature , increased utility and a prerequisite for reduced concentrations of sample reagents . miniaturised assemblies can be designed to perform a wide range of tasks that range from detecting airborne toxins to analysing dna and protein sequences . therefore , microfluidics systems provide a real potential for improving the efficiency of techniques applied in drug discovery and diagnostics . in order for microfluidic technology to interface with , and provide improvements for , current assaying techniques it needs to be adaptable . typical devices include passive flow systems , such as the passive fluid control ( pfc ) micro fluid analysis system by biomicro systems . pfc incorporates ' building block - like ' components into circuit designs in order to carry out sample processing , e.g. immobilisation , mixing , incubation . essentially , pfc utilises hydrophobicity and ' passive valves ' ( a narrowing of capillaries ) to control the movement of small volumes of fluids ( < 1 l ) within a network of channels . incorporation of active or passive pumps can also be used to control the movement of fluids in microfluidic systems , e.g. nanostream 's snap - n - flow system . a further setup by gyros   has integrated a cd element with the movement and control of nanolitre volumes . when the cd is set spinning centrifugal forces are created allowing the device to be used to produce a controlled passage of samples through ' microfabricated units ' on the surface of the cd . microfluidics systems capable of assaying ' unprocessed ' biological samples , e.g. blood , have been developed therefore eliminating the requirement for sample preparation , e.g. micronics . micronics ' microflow system can be used to extract analytes directly from whole blood and other particulate suspensions ( 5200 l volumes ) . the system utilises disposable ' lab cards ' , e.g. the activeh card can be used for sample preparation and isolation whereas the activet card can be used in immunoassays . some specific microfluidic systems have been developed that are capable of a range of dna - type analyses . a microfluidic integrated system , which minimises sample processing and handling , has been developed for pcr analysis . here dna typing is achieved from whole blood samples using capillary microfluidics and capillary array electrophoresis , see figure 1 , whereby blood is used directly as the sample template for a pcr amplification analysis . microfluidics technology has also illustrated a potential to be allied with the detection of very low numbers of dna molecules , i.e. potentially individual molecules . have shown that the construction of fluidic channels of < 1 m enables the detection and relative proportions of mixtures of dna molecules to be measured . in addition , using an electrical field to control the flow rates analysis times of only several milliseconds per dna molecule become achievable . electrophoretic mobility shift assays for the detection of dna - protein interactions have also been carried out in a microfluidic chip environment . some of the benefits achieved are reduced sample volumes , an avoidance of labelling procedures and decreased analysis times . however , the technique generally relies on passive diffusion of the sample volume , containing the target analytes , towards the immobilised probe elements and this can result in long hybridisation times ( normally hours ) . a method of accelerating the hybridisation time for dna arrays using plastic microfluidic chips , comprising networks of microfluidics channels plus an integrated pump , have been developed . it has been shown that ' high initial hybridisation velocities ' can be attained and that equilibrium , in terms of bound versus free analyte , is quickly achieved and so negates the requirement for such long hybridisation events . the assembly of arrays into microfluidic channels in order to improve the kinetics associated with hybridisation has also been shown by other researchers . a low - density array , generated within microfluidics channels , has been used to detect gene fragments ( k - ras ) carrying a point mutation . again it was found that microfluidics reduced the hybridisation time in this assay from hours , i.e. the time required in conventional static hybridisations , down to less than 1 minute . an alternative method of reducing array hybridisation times based on cavitation microstreaming has also been shown . essentially cavitation microstreaming involves the use of a sound field to induce the vibration of air - bubbles ( at a solid surface ) present within a fluid . this ultimately causes a circulatory flow within the fluid and so mixing times become reduced from hours to seconds . microfluidic technology has also been incorporated into the analysis of proteins / peptides . in particular , microfluidics can be linked with a mass spectrometric analysis of proteins or peptides . thus , peptides can be adsorbed onto hydrophobic membranes , desalted , and through the use of microfluidics eluted in a controlled manner to allow the direct mass spectrometric analysis of picomole amounts of peptides by electrospray ionisation mass spectrometry procedures , figure 2 . proteins are applied directly to a membrane , desalted and directed by microfluidic channel to mass spectrometric analysis . the recently reported combinatorial peptidomics approach   is also perfectly suited for use with integrated microfluidic systems and in principle allows identification of tryptic peptides directly from the crude proteolytic digest . combinatorial peptidomics initially utilises peptidomics where a protein sample is proteolytically digested prior to assaying , and combines it with a combinatorial depletion of the digest ( peptide pool ) by chemical cross - linking via amino acid side chains to allow a subsequent profiling of the resulting sample , figure 3 . sample solubilisation and protein purification are not necessary , since proteolyric digection may be carried on native cells / tissues ( dashed lines ) . the amino acid filtering ( depletion ) step may be repeated using combinations of up to 6 amino acid " filters " , i.e. chemically reactive surfaces ( e.g. derivatised beads ) able to covalently cross - link particular amino - acids . chemical depletion reduces the complexity of the peptide pool to a sufficient degree to make it compatible with direct ms detection . this allows the amount of protein delivered to the membrane , the reaction temperature within the device and the reaction time to be directly controlled for optimal digestion . thus , using microfluidics the sample can be supplied directly from upstream processing procedures , e.g. purification products from cell lysates . the development of protein microarray methods [ 12 - 14 ] , analogous to dna microarray technologies , for protein / peptide analysis has the potential to hasten the discovery of proteins of pharmacological value . as is the case with dna microarrays it is important that sample volumes required for analysis are low , the sensitivity of the assay is high ( particularly for low - abundance proteins ) , and hybridisation times are kept to a minimum in order to produce an efficient assay . a system incorporating protein microarrays , fluorescent detection and integrated microfluidics using planar waveguide technology has been developed . in combination these components enable quantitative measurements for protein profiling to be carried out with high sensitivity and also require shorter analysis times than static hybridisations . finally , more novel uses for microfluidic technology at a cellular level include the handling of mammalian embryos , the manipulation of embryos and oocytes in assisted reproduction   and even the isolation of motile spermatozoa . it is evident that the inherent flexibility of microfluidic systems will allow them to permeate and advance the development of assays in multiple biological , chemical and physical disciplines . thus , microfluidics should ultimately reduce the cost of running assays , decrease procedural times and limit the required concentration and hands - on manipulation of samples . rb acknowledges the support from the research strategy fund , royal holloway univesity of london .
microfluidics enables biotechnological processes to proceed on a scale ( microns ) at which physical processes such as osmotic movement , electrophoretic - motility and surface interactions become enhanced . at the microscale sample volumes and assay times are reduced , and procedural costs are lowered . 
 the versatility of microfluidic devices allows interfacing with current methods and technologies . 
 microfluidics has been applied to dna analysis methods and shown to accelerate dna microarray assay hybridisation times . 
 the linking of microfluidics to protein analysis techologies , e.g. mass spectrometry , enables picomole amounts of peptide to be analysed within a controlled micro - environment . 
 the flexibility of microfluidics will facilitate its exploitation in assay development across multiple biotechnological disciplines .