Microfluidic Flow Control

A novel 24-channel HPLC by Nanostream called Veloce was introduced at PITTCON 04. The column cassette contains 24 parallel microbore columns. The eluted samples are detected by a 24-channel UV filter photometer. The advantage of such a system is that it allows one to work with multiple samples simultaneously. Other interesting systems for parallel HPLC were those introduced by Eksigent, based on microfluidic flow control, and Sepiatec GmbH, which allows the processing of 75 multiple-well plates. 

Yoshida et al. [55] and Nakano et al. [73] tested ER effects in SU-8 channels with indium tin oxide electrodes, for self-control of ERF in hard substrates. Niu et al. designed a GERF-based microfluidic valve responsive to external DC signals and was able to develop this concept as a system for microfluidic flow control free of any limitations of flow type [74]. 

FIGURE 40.7 Characteristic frequencies could be shifted by an order of magnitude by locally altering PDMS membrane thicknesses ( fluidic capacitors ). Different curves represent different combinations of the thicknesses of two fluidic capacitor components in the same fluidic network. These fluidic bandpass filters provide the proof-of-concept of a new paradigm in microfluidic flow control, where actuation frequency could be used to passively control relative flow rates. 

Low YY et al (2001) Multichannel catalyst-testing reactor with microfluidic flow control. Chem big Tech 73(6) 661... 

Figure 4.22 Schematic of a pumping system based on a pneumatic gas pressure amplifier with microfluidic flow control via feedback from a sensitive flowmeter. In this way the flow rate is maintained regardless of changes in system back pressure or mobile phase viscosity, and changes in flow rates can be established rapidly and accurately, (a) A gradient system in which the mobile phase composition is controlled via flow rates of both mobile phase solvents, (b) A gradient system in which both back pressures and flow rates are monitored volume flow rates = k. (P(- -P ) and Ug = kg.(Pc - Pg) where k and kg are calibration constants, (c) A demonstration of the precision and accuracy with which controlled flow rates can be changed rapidly at total flow rates in the nL.min range, suitable for packed capillary HPLC. Reproduced from company literature (Eksigent 2005, 2006) with permission from Eksigent LLC.

Markov D A, Manuel S, Shot L M et al. (2010) Tape underlayment rotary-node (TURN) valves for simple on-chip microfluidic flow control. Biomedical Microdevices 135-144 DOI 10.1007/s10544-009-... 

The focus of the examples given in this chapter is clearly on micro reactors for chemical processing in contrast to p-TAS or Lab-Chip systems for bioanalytical applications. In the latter microfluidic systems, the fluidic requirements are somehow different from those in micro reactors. Typically, throughput plays only a minor role in p-TAS systems, in contrast to micro reactors, where often the goal is to achieve a maximum molar flux per unit volume of a specific product. Moreover, flow control plays a much greater role in p-TAS systems than in micro reactors. In... 

Fig. 2.6.10 Specialized experimental set-up for microfluidic flow dispersion measurements. Fluid is supplied from the top, flows via a capillary through the microfluidic device to be profiled and exits at the bottom. The whole apparatus is inserted into the bore of a superconducting magnet. Spatial information is encoded by MRI techniques, using rf and imaging gradient coils that surround the microfluidic device. They are symbolized by the hollow cylinder in the figure. After the fluid has exited the device, it is led through a capillary to a microcoil, which is used to read the encoded information in a time-resolved manner. The flow rate is controlled by a laboratory-built flow controller at the outlet [59, 60].

Microsystems are also expected to be introduced in the near future, including for example artificial noses, fingerprint sensing systems, bar code readers, rf-tag-ging systems, microfluidic pumps and dosing systems, gas flow control systems, new flexible and low cost displays or electronic paper. 

Several techniques for miniaturization of simple chemical and medical analysis systems are described. Miniaturization of total analysis systems realizes a small sample volume, a fast response and reduction of reagents. These features are useful in chemical and medical analysis. During the last decade many micro flow control devices, as well as the micro chemical sensors fabricated by three dimensional microfabrication technologies based on photofabrication, termed micromachining, have been developed. Miniaturized total analysis systems (pTAS) have been studied and some prototypes developed. In microfabricated systems, microfluidics , which represent the behavior of fluids in small sized channels, are considered and are very important in the design of micro elements used in pTAS. In this chapter microfluidics applied flow devices, micro flow control devices of active and passive microvalves, mechanical and non-mechanical micropumps and micro flow sensors fabricated by micromachining are reviewed. 

In this chapter, first the simple pTAS concepts for chemical and medical analysis using mechanical micro components are presented. Micro components of pTAS considering the microfluidics are described next. The micro flow control devices of microvalves, micropumps and micro flow sensors are then reviewed. 

The liquid pumping in the microfluidic chip is mostly achieved by using electro-osmotic flow (EOF) [324]. Other liquid pumping methods have also been employed for microfluidic flow. Flow has been employed for fraction collection and generation of concentration gradient. Laminar flow in the microfluidic channel allows liquid-liquid extraction and microfabrication to occur within the channels. Moreover, valving and mixing are needed in order to achieve a better flow control. All these microfluidic flow operations are further described in subsequent sections. 

FIGURE 7.41 Picture of the microfabricated fluidic device integrated with a standard MALDI-TOF sample plate. Because of the self-activating character of the microfluidic device, the system can be introduced into the MALDI ionization chamber without any wire or tube for the sample introduction and the flow control [820]. Reprinted with permission from the American Chemical Society. 

Chien, R.L., Parce, W.J., Multiport flow-control system for lab-on-a-chip microfluidic devices. Fres. J. Anal. Chem. 2001, 371(2), 106-111. 

Yu, C., Mutlu, S., Selvaganapathy, P., Mastrangelo, C.H., Svec, E, Frechet, J.M.J., Flow control valves for analytical microfluidic chips without mechanical parts based on thermally responsive monolithic polymers. Anal. Client. 2003, 75, 1958-1961. 

Buch, J.S., Wang, P.-C., DeVoe, D.L., Lee, C.S., Field-effect flow control in a polydimethylsiloxane-based microfluidic system. Electrophoresis 2001, 22(18), 3902-3907. 

The book is divided into several chapters which include micromachining methods, microfluidic operations (microfluidic flow, sample introduction, sample preconcentration), chemical separations, detection technology, and various chemical and biochemical analysis (applications on cellular analysis, nucleic acid analysis, and protein analysis). Emphasis will be placed on analytical applications although the basic principles about micromachining and fluid flow and control will also be covered only to the extent that their understanding will assist the exploitation of the microfluidic technology on analytical applications. 

GlaxoSmithKline Pharmaceuticals in Harlow, UK, performed the Hantzsch synthesis of 2-bromo-4 -methylacetophenone and l-acetyl-2-thiourea in NMP (N-methyl-2-pyrrolidone) using a microchip reador under EOF conditions [10] (for EOF see [11]) [10] This is claimed to be the first example of a heated organic reaction performed on a glass chip reactor under electroosmotic flow control, whereas only room temperature reactions were made earlier. In a wider scope, the Hantzsch synthesis is a further example to evaluate the potential of microfluidic systems for high-throughput... 

Qualitatively, the operation of the microfluidic flow-focusing system can be described in the following way. Two immiscible phases (e.g. Nitrogen and water, or water and oil) are delivered via their inlet channels to the flow-focusing junction. In this junction, one central inlet channel, that delivers the fluid-to-be-dispersed (e.g. Nitrogen to be dispersed into bubbles) ends upstream of a small constriction (an orifice). From the sides of the central channel, two additional ones terminate upstream of the orifice. These side channels deliver the continuous fluid (e.g. aqueous solution of surfactant). It is important that these continuous phase wets the walls of the microfluidic device preferentially. Otherwise - if the fluid-to-be-dispersed - wets the walls, the resulting flows are erratic [16] and it becomes virtually impossible to form bubbles (droplets) in a reproducible and controllable process. 

T. Brenner, T. Glatzel, R. Zengerle, and J. Ducree, Frequency-dependent transversal flow control in centrifugal microfluidics, Lab on A Chip, vol. 5, no. 2, pp. 146-150, 2005. 

In a microfluidic chip, there are a number of wells at the ends of the microchannel branches. These wells provide not only reservoirs for samples and reagents, but also the connection of electrodes to liquid in the microchannels. The liquid flow control is realized by applying different voltages to different wells simultaneously. In this way one can control the flow rate, and let one solution flowing through a microchannel in the desired direction while keeping all other solutions stationary in their wells and channels. 

Recently, we described the first example of the coupling of a microfluidics device to a MALDI-TOF mass spectrometer, by integrating an on-chip microreaction unit with a MALDI-TOF standard sample plate.27 This allows (bio)chemical reactions to take place in the MALDI-TOF instrument. Since it is based on a pressure-driven fluidics handling method, using the vacuum in the ionization chamber of the MALDI-TOF-MS system, this approach avoids wires and tubes for feed and flow control. 

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