• Many diverse advantages of this technology for microbiology are listed below: • General single cell studies including growth[84][34] • Cellular aging: microfluidic devices
    such as the “mother machine” allow tracking of thousands of individual cells for many generations until they die[84] • Microenvironmental control: ranging from mechanical environment[85] to chemical environment[86][87] • Precise spatiotemporal
    concentration gradients by incorporating multiple chemical inputs to a single device[88] • Force measurements of adherent cells or confined chromosomes: objects trapped in a microfluidic device can be directly manipulated using optical tweezers
    or other force-generating methods[89] • Confining cells and exerting controlled forces by coupling with external force-generation methods such as Stokes flow, optical tweezer, or controlled deformation of the PDMS (Polydimethylsiloxane) device[89][90][91]
    • Electric field integration[91] • Plant on a chip and plant tissue culture[92] • Antibiotic resistance: microfluidic devices can be used as heterogeneous environments for microorganisms.

  • The integration of such columns allows for experiments to be run where materials were in low availability or very expensive, like in biological analysis of proteins.

  • This reduction in reagent volumes allows for new experiments like single-cell protein analysis, which due to size limitations of prior devices, previously came with great

  • Continuous-flow devices are adequate for many well-defined and simple biochemical applications, and for certain tasks such as chemical separation, but they are less suitable
    for tasks requiring a high degree of flexibility or fluid manipulations.

  • Cell behavior[edit] Main article: Microfluidic cell culture The ability to create precise and carefully controlled chemoattractant gradients makes microfluidics the ideal
    tool to study motility,[97] chemotaxis and the ability to evolve / develop resistance to antibiotics in small populations of microorganisms and in a short period of time.

  • ADE technology is a very gentle process, and it can be used to transfer proteins, high molecular weight DNA and live cells without damage or loss of viability.

  • Particle detection microfluidics[edit] One application area that has seen significant academic effort and some commercial effort is in the area of particle detection in fluids.

  • Typically, micro means one of the following features: • Small volumes (μL, nL, pL, fL) • Small size • Low energy consumption • Microdomain effects Typically microfluidic systems
    transport, mix, separate, or otherwise process fluids.

  • [114] Through the usage of fiber optic coupling, the device can be isolated from instrumentation, preventing irradiative damage and minimizing the exposure of lab personnel
    to potentially harmful radiation, something not possible on the lab scale nor with the previous standard of analysis.

  • Since the analysis of spent nuclear fuel involves extremely harsh conditions, the application of disposable and rapidly produced devices (Based on castable and/or engravable
    materials such as PDMS, PMMA, and glass[115]) is advantageous, although material integrity must be considered under specific harsh conditions.

  • [49] To tune fluid penetration in porous substrates such as paper in two and three dimensions, the pore structure, wettability and geometry of the microfluidic devices can
    be controlled while the viscosity and evaporation rate of the liquid play a further significant role.

  • Microfluidic-assisted magnetophoresis[edit] One major area of application for microfluidic devices is the separation and sorting of different fluids or cell types.

  • Integrated chips can also be fabricated from multiple different materials, including glass and polyimide which are quite different from the standard material of PDMS used
    in many different droplet-based microfluidic devices.

  • [123] Some other practical applications of integrated HPLC chips include the determination of drug presence in a person through their hair[124] and the labeling of peptides
    through reverse phase liquid chromatography.

  • These closed-channel systems are inherently difficult to integrate and scale because the parameters that govern flow field vary along the flow path making the fluid flow at
    any one location dependent on the properties of the entire system.

  • [31] micro fluid sensor Process monitoring capabilities in continuous-flow systems can be achieved with highly sensitive microfluidic flow sensors based on MEMS technology,
    which offers resolutions down to the nanoliter range.

  • [82] In addition, microfluidics-based devices, capable of continuous sampling and real-time testing of air/water samples for biochemical toxins and other dangerous pathogens,[83]
    can serve as an always-on “bio-smoke alarm” for early warning.

  • Microdroplets allow for handling miniature volumes (μl to fl) of fluids conveniently, provide better mixing, encapsulation, sorting, and sensing, and suit high throughput

  • Conversely, microfluidic-assisted magnetophoresis may be used to facilitate efficient mixing within microdroplets or plugs.

  • [108] Photonics Lab on a Chip (PhLOC)[edit] Due to the increase in safety concerns and operating costs of common analytic methods, the Photonics Lab on a Chip (PhLOC) is becoming
    an increasingly popular tool for the analysis of actinides and nitrates in spent nuclear waste.

  • Moreover, because each droplet can be controlled independently, these systems also have dynamic reconfigurability, whereby groups of unit cells in a microfluidic array can
    be reconfigured to change their functionality during the concurrent execution of a set of bioassays.

  • [citation needed] Open microfluidics[edit] The behavior of fluids and their control in open microchannels was pioneered around 2005 and applied in air-to-liquid sample collection[12][13]
    and chromatography.

  • This technique can be readily utilized in industrial settings where the fluid at hand already contains magnetically active material.

  • Other research has also shown that the label-free separation of cells may be possible by suspending cells in a paramagnetic fluid and taking advantage of the magneto-Archimedes

  • This is where microfluidics can have an impact: The lithography-based production of microfluidic devices, or more likely the production of reusable molds for making microfluidic
    devices using a molding process, is limited to sizes much smaller than traditional machining.

  • Fuel cells[edit] Further information: Electroosmotic pump Microfluidic fuel cells can use laminar flow to separate the fuel and its oxidant to control the interaction of the
    two fluids without the physical barrier that conventional fuel cells require.

  • [114] Through the development of a spectrophotometric approach to analyzing spent fuel, an on-line method for measurement of reactant quantities is created, increasing the
    rate at which samples can be analyzed and thus decreasing the size of deviations detectable within reprocessing.

  • [140][144] An example in food engineering research is a novel micro-3D-printed device fabricated to research production of droplets for potential food processing industry
    use, particularly in work with enhancing emulsions.

  • These methods are being researched because they use less reactants, space, and time compared to traditional techniques such as liquid chromatography.

  • [28][79] The basic idea of microfluidic biochips is to integrate assay operations such as detection, as well as sample pre-treatment and sample preparation on one chip.

  • [29][30] Continuous-flow microfluidic operation is the mainstream approach because it is easy to implement and less sensitive to protein fouling problems.

  • The main advantage of integrating HPLC columns into microfluidic devices is the smaller form factor that can be achieved, which allows for additional features to be combined
    within one microfluidic chip.

  • However, recently other techniques for droplet manipulation have also been demonstrated using magnetic force,[45] surface acoustic waves,[46] optoelectrowetting, mechanical
    actuation,[47] etc.

  • [41] Digital microfluidics[edit] Main article: Digital microfluidics Alternatives to the above closed-channel continuous-flow systems include novel open structures, where
    discrete, independently controllable droplets are manipulated on a substrate using electrowetting.

  • [145] Paper and droplet microfluidics allow for devices that can detect small amounts of unwanted bacteria or chemicals, making them useful in food safety and analysis.

  • Each of these methods has its own associated techniques to maintain robust fluid flow which have matured over several years.

  • Techniques such as droplet microfluidics are used to create emulsions that are more controlled and complex than those created by traditional homogenization due to the precision
    of droplets that is achievable.

  • This feature makes the technology suitable for a wide variety of applications including proteomics and cell-based assays.

  • Another advantage of open microfluidics is the ability to integrate open systems with surface-tension driven fluid flow, which eliminates the need for external pumping methods
    such as peristaltic or syringe pumps.

  • [118][119] This is an important feature because different applications of HPLC microfluidic chips may call for different pressures.

  • [1] It has practical applications in the design of systems that process low volumes of fluids to achieve multiplexing, automation, and high-throughput screening.

  • [121] The coupling of HPLC-chip devices with other spectrometry methods like mass-spectrometry allow for enhanced confidence in identification of desired species, like proteins.

  • [8][9] Various kinds of microfluidic flows Microfluidic flows need only be constrained by geometrical length scale – the modalities and methods used to achieve such a geometrical
    constraint are highly dependent on the targeted application.

  • Active microfluidics refers to the defined manipulation of the working fluid by active (micro) components such as micropumps or microvalves.

  • [122] Microfluidic chips have also been created with internal delay-lines that allow for gradient generation to further improve HPLC, which can reduce the need for further

  • Often, processes normally carried out in a lab are miniaturised on a single chip, which enhances efficiency and mobility, and reduces sample and reagent volumes.

  • [111] Measurements made with these methods have been validated at the bulk level for industrial tests,[109][112] and are observed to have a much lower variance at the micro-scale.

  • [116] The early methods had the advantage of easier detection from certain machines like those that measure fluorescence.

  • [32] Droplet-based microfluidics[edit] Main article: Droplet-based microfluidics High frame rate video showing microbubble pinch-off formation in a flow-focusing microfluidic
    device[33] Droplet-based microfluidics is a subcategory of microfluidics in contrast with continuous microfluidics; droplet-based microfluidics manipulates discrete volumes of fluids in immiscible phases with low Reynolds number and laminar
    flow regimes.

  • [51] Current applications include portable glucose detection[52] and environmental testing,[53] with hopes of reaching areas that lack advanced medical diagnostic tools.

  • [95] Other applications include various electrophoresis and liquid chromatography applications for proteins and DNA, cell separation, in particular, blood cell separation,
    protein analysis, cell manipulation and analysis including cell viability analysis[34] and microorganism capturing.

  • Various applications rely on passive fluid control using capillary forces, in the form of capillary flow modifying elements, akin to flow resistors and flow accelerators.

  • [44] Many lab-on-a-chip applications have been demonstrated within the digital microfluidics paradigm using electrowetting.

  • [143] Although these methods have benefits, they currently lack the ability to be produced at large scale that is needed for commercialization.

  • [73][74] While this does eliminate the complexity of particle functionalization, more research is needed to fully understand the magneto-Archimedes phenomenon and how it can
    be used to this end.

  • [110] Likewise, the microfluidic technology developed for the analysis of spent nuclear fuel is predicted to expand horizontally to analysis of other actinide, lanthanides,
    and transition metals with little to no modification.

  • In addition, open microfluidics eliminates the need to glue or bond a cover for devices, which could be detrimental to capillary flows.

  • Many such devices feature hydrophobic barriers on hydrophilic paper that passively transport aqueous solutions to outlets where biological reactions take place.

  • [76] Additionally, microfluidic manufacturing advances mean that makers can produce the devices in low-cost plastics[77] and automatically verify part quality.

  • Microfluidic flow enables fast sample throughput, automated imaging of large sample populations, as well as 3D capabilities.

  • [147] In addition to paper-based methods, research demonstrates droplet-based microfluidics shows promise in drastically shortening the time necessary to confirm viable bacterial
    contamination in agricultural waters in the domestic and international food industry.

  • Particle detection of small fluid-borne particles down to about 1 μm in diameter is typically done using a Coulter counter, in which electrical signals are generated when
    a weakly-conducting fluid such as in saline water is passed through a small (~100 μm diameter) pore, so that an electrical signal is generated that is directly proportional to the ratio of the particle volume to the pore volume.


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