Chemical Amplification: Continuous-Flow PCR on a Chip

Kopp, Martin U.; Mello, Andrew J. de; Manz, Andreas

doi:10.1126/science.280.5366.1046

Cited by 1,198 publications

(843 citation statements)

References 9 publications

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“…Referred to as micro-Total Analysis Systems (m-TAS) or Lab-on-a-Chip (LOC), these devices perform techniques such as cell culturing, Fluorescence Activated Cell Sorting (FACS), 10 and Polymerase Chain Reaction (PCR) 11 on one small and disposable chip.…”

Section: Professor Luke P Lee Is L L O Y D D I S T I N G U I S H E Dmentioning

confidence: 99%

Microfluidics-based systems biology

2006

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Systems biology seeks to develop a complete understanding of cellular mechanisms by studying the functions of intra-and inter-cellular molecular interactions that trigger and coordinate cellular events. However, the complexity of biological systems causes accurate and precise systems biology experimentation to be a difficult task. Most biological experimentation focuses on highly detailed investigation of a single signaling mechanism, which lacks the throughput necessary to reconstruct the entirety of the biological system, while high-throughput testing often lacks the fidelity and detail necessary to fully comprehend the mechanisms of signal propagation. Systems biology experimentation, however, can benefit greatly from the progress in the development of microfluidic devices. Microfluidics provides the opportunity to study cells effectively on both a single-and multi-cellular level with high-resolution and localized application of experimental conditions with biomimetic physiological conditions. Additionally, the ability to massively array devices on a chip opens the door for high-throughput, high fidelity experimentation to aid in accurate and precise unraveling of the intertwined signaling systems that compose the inner workings of the cell.

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Section: Professor Luke P Lee Is L L O Y D D I S T I N G U I S H E Dmentioning

confidence: 99%

Microfluidics-based systems biology

2006

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“…The advantage of temperature is simple reversibility: the solution containing the released templates of DNA only needs to be cooled again to allow the next separation process to be performed. Problems in controlling many temperature jumps of 20°C or more on the scale of 0.1 mm or less, however, make the dense integration of this approach doubtful, despite the recent demonstration of chip-based PCR (Kopp et al, 1998). In the case of chemical hybridization control, the other factors must be removed, either physically or chemically, to allow the released DNA to rehybridize.…”

Section: Selection Transfer Modulementioning

confidence: 99%

Optically programming DNA computing in microflow reactors

McCaskill¹

2001

Biosystems

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The programmability and the integration of biochemical processing protocols are addressed for DNA computing using photochemical and microsystem techniques. A magnetically switchable selective transfer module (STM) is presented which implements the basic sequence-specific DNA filtering operation under constant flow. Secondly, a single steady flow system of STMs is presented which solves an arbitrary instance of the maximal clique problem of given maximum size N. Values of N up to about 100 should be achievable with current lithographic techniques. The specific problem is encoded in an initial labeling pattern of each module with one of 2N DNA oligonucleotides, identical for all instances of maximal clique. Thirdly, a method for optically programming the DNA labeling process via photochemical lithography is proposed, allowing different problem instances to be specified. No hydrodynamic switching of flows is required during operation -the STMs are synchronously clocked by an external magnet. An experimental implementation of this architecture is under construction and will be reported elsewhere.

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“…There are two major types of miniaturized bioreaction systems: batch-based systems where the stationary reaction solution is heated or thermocycled inside a reaction chamber by either external heaters [3][4][5][6][7][8][9][10][11][12][13][14][15][16] or integrated on-chip heaters, [17][18][19][20][21][22][23][24] and continuous flow-based systems where the sample flows through certain temperature zones with well-defined flow rates. [25][26][27][28][29][30] Other novel approaches, such as on-chip rotary reaction, 31 noncontact infrared-mediated reaction, [32][33][34] electrokinetically synchronized reaction, 35 electrowetting-based reaction 36 and Rayleigh-Bénard convection-based reaction 37,38 have also been reported. Recent trends in miniaturized bioreaction systems are to integrate bioreactions with sample preparation, fluidic handling, and product detection to produce systems that can rapidly, conveniently, and economically extract information from raw biological samples with greatly reduced cost.…”

Section: Introductionmentioning

confidence: 99%

Microfabricated valveless devices for thermal bioreactions based on diffusion-limited evaporation

2008

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Microfluidic devices that reduce evaporative loss during thermal bioreactions such as PCR without microvalves have been developed by relying on the principle of diffusion-limited evaporation. Both theoretical and experimental results demonstrate that the sample evaporative loss can be reduced by more than 20 times using long narrow diffusion channels on both sides of the reaction region. In order to further suppress the evaporation, the driving force for liquid evaporation is reduced by two additional techniques: decreasing the interfacial temperature using thermal isolation and reducing the vapor concentration gradient by replenishing water vapor in the diffusion channels. Both thermal isolation and vapor replenishment techniques can limit the sample evaporative loss to approximately 1% of the reaction content.

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Chemical Amplification: Continuous-Flow PCR on a Chip

Cited by 1,198 publications

References 9 publications

Microfluidics-based systems biology

Microfluidics-based systems biology

Optically programming DNA computing in microflow reactors

Microfabricated valveless devices for thermal bioreactions based on diffusion-limited evaporation

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