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This article reviews state-of-the-art microfluidic biosensors of nucleic acids and proteins for pointof-care (POC) diagnostics. Microfluidics is capable of analyzing small sample volumes (10 -9 -10 -18 l) and minimizing costly reagent consumption as well as automating sample preparation and reducing processing time. The merger of microfluidics and advanced biosensor technologies offers new promises for POC diagnostics, including high-throughput analysis, portability and disposability. However, this merger also imposes technological challenges on biosensors, such as high sensitivity and selectivity requirements with sample volumes orders of magnitude smaller than those of conventional practices, false response errors due to non-specific adsorption, and integrability with other necessary modules. There have been many prior review articles on microfluidic-based biosensors, and this review focuses on the recent progress in last 5 years. Herein, we review general technologies of DNA and protein biosensors. Then, recent advances on the coupling of the biosensors to microfluidics are highlighted. Finally, we discuss the key challenges and potential solutions for transforming microfluidic biosensors into POC diagnostic applications.

ABSTRACT--Because the nature of failure in concrete is complicated due to the material heterogeneity, a robust measuring method is essential to obtain reliable deformation data.A nondestructive displacement evaluation system using a digital image cross-correlation scheme, often called computer vision, is developed to make microscopic examinations of the fracture processes in concrete. This is a full-field measuring method that gives an accuracy within the micron range for a 100 mm x 75 mm viewing area. A feedback signal that combines the lateral and axial deformations provides a wellbalanced imaging rate both before and after the peak load. Displacement vector diagrams or displacement contour maps of concrete reveal highly nonuniform deformations even in the elastic range. The processes of fracture in concrete are well defined at different deformation levels.

We report a MEMS (Micro-Electro-Mechanical Systems)-based microbial fuel cell (MFC) that produces a high power density. The MFC features 4.5-μL anode/cathode chambers defined by 20-μm-thick photo-definable polydimethylsiloxane (PDMS) films. The MFC uses a Geobacter-enriched mixed bacterial culture, anode-respiring bacteria (ARB) that produces a conductive biofilm matrix. The MEMS MFC generated a maximum current density of 16,000 μA cm(-3) (33 μA cm(-2)) and power density of 2300 μW cm(-3) (4.7 μW cm(-2)), both of which are substantially greater than achieved by previous MEMS MFCs. The coulombic efficiency of the MEMS MFC was at least 31%, by far the highest value among reported MEMS MFCs. The performance improvements came from using highly efficient ARB, minimizing the impact of oxygen intrusion to the anode chamber, having a large specific surface area that led to low internal resistance.

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Non-specific adsorption (NSA) of biomolecules is a persistent challenge in microfluidic biosensors. Microfluidic biosensors often have immobilized bioreceptors such as antibodies, enzymes, DNAs, etc, via linker molecules such as SAMs (self-assembled monolayers) to enhance immobilization. However, the linker molecules are very susceptible to NSA, causing false responses and decreasing sensitivity. In this paper, we present design methods to reduce the NSA of alkanethiol SAMs, which are popular linker molecules on microfluidic biosensors. Three design parameters were studied for two different chain-length SAMs (n = 2 and 10): (i) SAM incubation time, (ii) surface roughness [0.8 nm and 4.4 nm RMS (root mean square)] and (iii) gold crystal re-growth along (1 1 1) the target orientation. NSA was monitored by surface plasmon resonance (SPR). The results suggest that increased SAM incubation time reduces NSA, and that short-chain SAMs respond more favorably than the long-chain SAMs. Both SAMs were shown to be sensitive to surface roughness, and long-chain SAMs reduced NSA by 75%. Gold crystal re-growth along (1 1 1) the target orientation profoundly reduced NSA on the short-chain SAM. On a gold surface where surface roughness was 0.8 nm and there was strong directional alignment along the (1 1 1) gold crystal, final concentrations of nonspecifically bound proteins were 0.05 ng mm −2 (fibrinogen) and 0.075 ng mm −2 (lysozyme)-significantly lower than other known methods. The results show that optimizing three parameters (SAM incubation time, gold surface roughness and gold crystal orientation) improved SAM sensitivity for fibrinogen-anti-fibrinogen conjugates by a factor of 5 in 2.94 pM, suggesting that the methods are effective for reducing NSA in microfluidic biosensors.

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