Microfabricated reaction and separation systems

Department of Chemical Engineering, University of Michigan, 2300 Hayward, 3022 HH Dow, Ann Arbor, MI 48109-2136, USA.
Current Opinion in Biotechnology (Impact Factor: 7.12). 03/2001; 12(1):92-8. DOI: 10.1016/S0958-1669(00)00166-X
Source: PubMed


Over the past year there have been a number of recent advances in the fields of miniaturized reaction and separation systems, including the construction of fully integrated 'lab-on-a-chip' systems. Microreactors, which initially targeted DNA-based reactions such as the polymerase chain reaction, are now used in several other chemical and biochemical assays. Miniaturized separation columns are currently employed for analyzing a wide variety of samples including DNA, RNA, proteins and cells. Although significant advances have been made at the component level, the realization of an integrated analysis system still remains at the early stages of development.

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Available from: Rohit Pal, Mar 25, 2015
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    • "There is considerable literature regarding the use of embossed components in micro devices, and they tend to fall into the following broad categories: • Micro reactors e.g. [1] [2] • Micro fluidic flow systems for physical separation [3] [4] • Micro optical devices [5] [6] In all cases the product performance depends upon creating patterns or features in a polymer workpiece that have characteristic dimensions in the 0.1 to 100 µm range. There is currently a move to net shape forming (e.g. "
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    ABSTRACT: A promising technique for the large-scale manufacture of micro-fluidic devices and photonic devices is hot embossing of polymers such as PMMA. Micro-embossing is a deformation process where the workpiece material is heated to permit easier material flow and then forced over a planar patterned tool. While there has been considerable, attention paid to process feasibility very little effort has been put into production issues such as process capability and eventual process control. In this paper, we present initial studies aimed at identifying the origins and magnitude of variability for embossing features at the micron scale in PMMA. Test parts with features ranging from 3.5- 630 µm wide and 0.9 µm deep were formed. Measurements at this scale proved very difficult, and only atomic force microscopy was able to provide resolution sufficient to identify process variations. It was found that standard deviations of widths at the 3-4 µm scale were on the order of 0.5 µm leading to a coefficient of variation as high as 13%. Clearly, the transition from test to manufacturing for this process will require understanding the causes of this variation and devising control methods to minimize its magnitude over all types of parts. Singapore-MIT Alliance (SMA)
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    • "In some instances, the target DNA may be released by elevated temperatures simultaneously during the denaturing step of the amplification protocol (Belgrader et al., 1999). The amplification of DNA is typically performed by the polymerase chain reaction (PCR) (Kuske et al., 1998; Wilding et al., 1998; Belgrader et al., 1999; Anderson et al., 2000; Khandurina et al., 2000; Pourahmadi et al., 2000; Lagally et al., 2001; Krishnan et al., 2001). Researchers have shown that strand displacement amplification (SDA) is also an effective procedure (Walker et al., 1992; Walker, 1993; Westin et al., 2000), in that it provides isothermal amplification and has the ability to multiplex with tethered templates and primers (Westin et al., 2000). "
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    ABSTRACT: An integrated, stacked microlaboratory for performing automated electric-field-driven immunoassays and DNA hybridization assays was developed. The stacked microlaboratory was fabricated by orderly laminating several different functional layers (all 76 x 76 mm(2)) including a patterned polyimide layer with a flip-chip bonded CMOS chip, a pressure sensitive acrylic adhesive (PSA) layer with a fluidic cutout, an optically transparent polymethyl methacrylate (PMMA) film, a PSA layer with a via, a patterned polyimide layer with a flip-chip bonded silicon chip, a PSA layer with a fluidic cutout, and a glass cover plate layer. Versatility of the stacked microlaboratory was demonstrated by various automated assays. Escherichia coli bacteria and Alexa-labeled protein toxin staphylococcal enterotoxin B (SEB) were detected by electric-field-driven immunoassays on a single chip with a specific-to-nonspecific signal ratios of 4.2:1 and 3.0:1, respectively. Furthermore, by integrating the microlaboratory with a module for strand displacement amplification (SDA), the identification of the Shiga-like toxin gene (SLT1) from E. coli was accomplished within 2.5 h starting from a dielectrophoretic concentration of intact E. coli bacteria and finishing with an electric-field-driven DNA hybridization assay, detected by fluorescently labeled DNA reporter probes. The integrated microlaboratory can be potentially used in a wide range of applications including detection of bacteria and biowarfare agents, and genetic identification.
    Biosensors & Bioelectronics 07/2002; 17(6-7):605-18. DOI:10.1016/S0956-5663(02)00023-4 · 6.41 Impact Factor
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    • "Though electrochemical detectors offer some attractive features (high sensitivity, tunable selectivity combined with low volumes), they are still not state of the art in combination with micro¯uidic devices. CL has been proven to allow sensitive detection of metal ions or in immunoassays [11], for example, and is particularly attractive for microanalytical systems as no light source is required leading to simpler instruments [1]. The aim of this work was to investigate possibilities for the determination of a non-¯uorescent compound, using an enzymatic assay together with CL detection and comparing solved and immobilised enzymes on the one hand, and electrophoretic separation with indirect ¯uorescence detection on the other. "
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    ABSTRACT: This report describes general investigations for xanthine determination in microfluidic devices. Xanthine is chosen as a model analyte for the detection of compounds via bi-enzymatic systems on one hand, and via capillary electrophoresis (CE) of non-fluorescent analytes on the other. The bi-enzyme system comprises xanthine oxidase (XOD) and horseradish peroxidase (HRP) with XOD giving the specificity for the analyte and HRP allowing chemiluminescent (CL) detection. Studies include the use of enzyme solutions, as well as enzyme coated beads pumped continuously through the device or trapped in a 330 pL cavity. In a second approach, indirect laser-induced fluorescence (LIF) is used as a detection method for microchip-based CE separations. Although the detection methods are not optimised, this report demonstrates general new possibilities for a fast determination of such compounds, in particular xanthine, in microfluidic devices.
    Sensors and Actuators B Chemical 01/2002; 81(2-3-81):369-376. DOI:10.1016/S0925-4005(01)00963-7 · 4.10 Impact Factor
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