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Integrated Microfluidic Systems for DNA Analysis

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Microfluidics

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 304))

Abstract

The potential utility of genome-related research in terms of evolving basic discoveries in biology has generated widespread use of DNA diagnostics and DNA forensics and driven the accelerated development of fully integrated microfluidic systems for genome processing. To produce a microsystem with favorable performance characteristics for genetic-based analyses, several key operational elements must be strategically chosen, including device substrate material, temperature control, fluidic control, and reaction product readout. As a matter of definition, a microdevice is a chip that performs a single processing step, for example microchip electrophoresis. Several microdevices can be integrated to a single wafer, or combined on a control board as separate devices to form a microsystem. A microsystem is defined as a chip composed of at least two microdevices. Among the many documented analytical microdevices, those focused on the ability to perform the polymerase chain reaction (PCR) have been reported extensively due to the importance of this processing step in most genetic-based assays. Other microdevices that have been detailed in the literature include those for solid-phase extractions, microchip electrophoresis, and devices composed of DNA microarrays used for interrogating DNA primary structure. Great progress has also been made in the areas of chip fabrication, bonding and sealing to enclose fluidic networks, evaluation of different chip substrate materials, surface chemistries, and the architecture of reaction conduits for basic processing steps such as mixing. Other important elements that have been developed to realize functional systems include miniaturized readout formats comprising optical or electrochemical transduction and interconnect technologies. These discoveries have led to the development of fully autonomous and functional integrated systems for genome processing that can supply “sample in/answer out” capabilities. In this chapter, we focus on microfluidic systems that are composed of two or more microdevices directed toward DNA analyses. Our discussions will primarily be focused on the integration of various processing steps with microcapillary electrophoresis (μCE) or microarrays. The advantages afforded by fully integrated microfluidic systems to enable challenging applications, such as single-copy DNA sequencing, single-cell gene expression analysis, pathogen detection, and forensic DNA analysis in formats that provide high throughput and point-of-analysis capabilities will be discussed as well.

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Abbreviations

AOM:

Aluminum oxide membranes

BPU:

Biochemical processing unit

CAE:

Capillary array electrophoresis

CFPCR:

Continuous flow polymerase chain reaction

COC:

Cyclic olefin copolymer

ddNTPs:

Dideoxy nucleoside triphosphates

DNA:

Deoxyribonucleic acid

dNTPS:

Deoxyribonucleotide triphosphate

DRIE:

Deep reactive ion etching

EDTA:

Ethylenediaminetetraacetic acid

ELFSE:

End-labeled free-solution electrophoresis

EOF:

Electroosmotic flow

FPC:

Flexible printed circuits

FSCE:

Free solution conjugate electrophoresis

HEC:

Hydroxyethyl cellulose

HGP:

Human genome project

ITO:

Indium–tin oxide

LDR:

Ligase detection reaction

LPA:

Linear polyacrylamides

MDR-TB:

Multidrug resistant tuberculosis

MHEC:

Methyl hydroxyethyl cellulose

PC:

Polycarbonate

PCR:

Polymerase chain reaction

PDMS:

Poly(dimethylsiloxane)

PEO:

Poly(ethylene oxides)

PMMA:

Poly(methyl methacrylate)

PPC:

Photoactivated polycarbonate

RNA:

Ribonucleic acid

RTD:

Resistance temperature detector

RT-PCR:

Reverse transcription polymerase chain reaction

SGE:

Slab gel electrophoresis

SPE:

Solid-phase extraction

STRs:

Short tandem repeats

TE:

Thermoelectric

TTE:

tris-Taps-EDTA

μCE:

Microcapillary electrophoresis

μTAS:

Micro-total analysis systems

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Njoroge, S.K., Chen, HW., Witek, M.A., Soper, S.A. (2011). Integrated Microfluidic Systems for DNA Analysis. In: Lin, B. (eds) Microfluidics. Topics in Current Chemistry, vol 304. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_153

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