Laminar flow platform

The laminar flow platform comprises liquid handling and (bio-) chemical assay principles, based on the stable hydrodynamic conditions in pressure driven laminar flows through microchannels. The samples are processed by injecting them into the chip inlets using external pumps or pressure sources, either batch-wise or in a continuous mode. 

The basic unit operation on the pressure driven laminar flow platform is the contacting of at least two liquid streams at a microfluidic channel junction (see Fig. 7). This leads to controlled difflisional mixing at the phase interface, e g. for initiation of a (bio-) chemical reaction [105]. It can also be applied for the lateral focusing of micro-objects like particles or cells in the channel [95]. The required flow focusing channel network consists of one central and two S5munetric side channels, connected at a junction to form a common outlet channel. By varying the ratio of the flow rates, the lateral width of the central streamline within the common outlet channel can be adjusted very accurately. Consequently, micro-objects suspended in the liquid flowing... 

Figure 7. Contacting on the laminar flow platform. Three different liquid streams are symmetrically contacted at an intersection point. This microfluidic structure is also referred to as flow focusing structure [95],...

A great number of valving principles exists on the pressure driven laminar flow platform, summarized in a review by Oh and Ahn [38]. Active as well as passive solutions have been presented. However, no standards have emerged so far, so the choice and implementation of valves remains a difficulty on this platform. A possible approach is to transfer the valving functionality off-chip [113], thus decreasing the complexity and cost of the disposable. 

The pressure driven laminar flow platform is especially interesting for online monitoring applications, since it enables continuous flows compared to the merely batch-wise operation of most of the other microfluidic platforms (i.e. handling discrete liquid volumes). 

M. Karle, J. Miwa, G. Roth, R. Zengerle, and F. von Stetten, A Novel Microfluidic Platform for Continuous DNA Extraction and Purification Using Laminar Flow Magnetophoresis, 2009, pp. 276-279. 

Microfluidics, by contrast, allows for temporal and spatial control over the soluble microenvironment because of the nature of laminar flow [30, 31, 72]. Other parameters also affect the soluble factor signalling, such as cell density, exogenous growth factors, medium change frequency or even culture platforms... 

Tlie technological requiiements for designing and constructing microfluidic devices for micro- and nano-technology ai e expanding. A microfluidic platform for the constraction of microscale components and autonomous systems consists of a combination of liquid-phase photopolynierization, lithography, and laminar flow to generate channels, valves, actuators, sensors, and systems. " ... 

The laminar flow restriction and small dimensions of microfluidic devices have been exploited to expose different portions of a single cell to different chemical environments. A method developed by Whitesides and coworkers utilized hydrodynamic focusing on a microfluidic platform to selectively label portions of a cell with different dyes (Figure 32.15). Laminar fluid flow confined the dye solution to particular regions of the channel despite being in contact with streams containing... 

DeBusschere and Kovacs [28] developed a portable microfluidic platform integrated with a complementary metal-oxide semiconductor (CMOS) chip which enables control of temperature as well as the capacity to measure action potentials in cardiomyocytes. When cells were stimulated with nifedipine (a calcium channel blocker), action potential activity was interrupted. Morin et al. [29] seeded neurons in an array of chambers in a microfluidic network integrated with an array of electrodes (Fig. 5b). The electrical activity of cells triggered with an electrical stimulus was monitored for several weeks. Cells in all chambers responded asynchronously to the stimulus. This device illustrates the utility of microfluidic tools that can investigate structure, function, and organization of biological neural networks. A similar study probed the electrical characteristics of neurons as they responded to thermal stimulation [30] in a microfluidic laminar flow. Neurons were seeded on an array of electrodes (Fig. 5c) which allowed for measurements of variations in action potentials when cells were exposed to different temperatures. 

Disadvantages of conventional microchips include resistance to hydrodynamic flow (backpressure), adsorption of some biomolecules on walls, and limited robustness (e.g., clogging narrow channels). Digital microfluidic systems overcome the problems with mixing reagents, which are normally associated with conventional microfluidic devices that use laminar hydrodynamic flow. Such microscale platforms are normally based on the electrowetting-on-dielectric (EWOD) principle [66]. In these digital microchips. 

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