Microfluidic Functional Elements

In the context of proteomic applications, microfluidic devices must comprise all functional elements necessary to perform essential processing steps prior to MS detection, i.e. sample clean-up, preconcentration, affinity selection, digestion and separation. As a result, micropumps, valves, mixers, microreactors, 

Pressure-driven separations such as LC, that have demonstrated performance for the separation of peptide mixtures and that enable the loading of large sample amounts, have gained widespread popularity in proteomic applications. In addition, LC eluent compositions are fully compatible with electrospray MS ion sources, making this technique a clearly superior alternative to electrically driven separations which necessitate high-concentration buffer systems that are incompatible with ESI-MS. The proteomic/biomarker chips that are described in this work comprise fully integrated LC systems.33 

Adapted with permission from Anal. Chem., 2006, 78(15), 5513-5524. 

Microfluidic Bioanalytical Platforms with Mass Spectrometry 

Fluidic propulsion on the LC chips can be accomplished using an EOF pumping/valving approach.33,34 Electrically driven flows are routinely utilized 

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Microfluidic devices that use electrical fields for fluidic propulsion perform successfully for a variety of electrically driven separations, and thus, present unique opportunities to the analytical and biomedical community. The availability of a broad range of microfluidic functional elements, materials, and processes facilitated the miniaturization of most types of electrically driven separations that use optical and electrochemical detection systems capillary electrochromatography... 

Figure 3 A sophisticated microfluidic device used for DNA processing. Numerous functional elements have been adapted for use with microfluidics, and it is now possible to perform virtually any combination of chemical processes in a microfluidic device.

Microfluidic devices comprise a variety of functional elements that perform operations such as, pumping, valving, dispensing, sample clean up, mixing, separation, chemical alterations and detection.7 These devices typically handle 1-5 pL of sample, and enable the analysis of volumes as low as 1 pL-1 nL. Sample injection, separation, labeling and detection are often performed in a time domain of a few minutes or seconds.10 A unique advantage of miniaturization is that a... 

A stand-alone microfluidic-MS platform that enabled us to survey protein expression at the global level and to identify a panel of five cancer-specific biomarkers was developed. The microfluidic chip comprised a series of functional elements that facilitated data-dependent LC-ESI-MS-MS analysis. The chip had a stand-alone configuration to favor the fabrication of multiplexed layouts for high-throughput investigations. 

Overall, current microfluidics is mature enough to provide the technology for protein analysis, including pretreatment and separation. Rather, it seems that biosensors with biological functional elements need significant progress to make contribution to practical protein research and practical applications. 

Methods for electrochemical, catalytic (metal assisted), and deep reactive ion etching (DRIE) of silicon have been developed, which enable fabrication of arrays of deep cylindrical or modulated pores, walls, tubes, combinations of these, and other forms with vertical walls (Wu et al. 2010). As a rule, the regular arrays produced by electrochemical etching are characterized by constant porosity and pore depths (up to 500 pm) and form a planar front propagating into the substrate. Various devices and functional elements for micromechanics, photonics, chemical power sources, microfluidics, photovoltaics, etc. (see Porous Silicon Application Survey chapter), are commonly fabricated on the basis of these arrays by post-anodization treatment intended to modify the structure and properties of macroporous silicon to raise or reduce its porosity, change the shape of pores, transform the pore array into a column array, change the properties of the inner surface of pores, coat it with the film of a metal or insulator, open up pores, fill pores with various fillers, dope the silicon walls, etc. Some procedures can be performed locally, which requires formation of a pattern and subsequent structuring. 

It is often desirable to immobilize different biomolecules on different sensing elements in close proximity on the same nanophotonic sensor in the development of a multiplexed sensor. This is the case in the example of parallel ID photonic crystal resonators described in Sect. 16.4. Cross-contamination of biomolecules must be avoided in order to preserve high specificity. We have found that a combination of parylene biopatteming and polydimethylsiloxane (PDMS) microfluidics is a convenient means to immobilized multiple biomolecules in close proximity without cross-contamination as shown in Fig. 16.8. Parylene biopatteming is first used to expose only the regions of highest optical intensity of the nanosensor for functionalization. Second, a set of PDMS microfluidics is applied to the parylene-pattemed nanophotonic sensor, and the biomolecules to be attached... 

Inside microfluidic channels the flow is laminar. Due to the absence of turbulences different media do not mix or mix only spontaneously and very slowly. Automatic elements can only operate correct in the presence of sufficient process medium. Otherwise, in the absence of stimulation, the control functionality can not be performed. Therefore, inside microfluidic channel networks the realisation of a recirculation is recommended which can provide an independency from the state (open or closed) of the active hydrogel components. 

Several modules had to be developed before a functional microfluidic HPLC system could be assembled. In a series of papers, the Sandia National Laboratory group demonstrated high-pressure connectors for introduction of liquids, fabrication of integrated polymer checking microvalve elements, on-chip high-pressure picoliter injector, and eventually a complete HPLC chip. ... 

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