Biomedical Engineering Reference
In-Depth Information
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Introduction
Microfluidics-based biochips, also referred to as lab-on-a-chip, are revo-
lutionizing many areas of biochemistry and biomedical sciences. Typical
applications include enzymatic analysis (e.g., lactate assays), DNA sequenc-
ing, immunoassays, proteomic analysis, blood chemistry for clinical diag-
nostics, and environmental toxicity monitoring [1-3]. These devices enable
the precise control of microliter and nanoliter volumes of biological samples.
They combine electronics with biology, and they integrate various bioassay
operations such as sample preparation, analysis, separation, and detection
[1,4]. Compared to conventional laboratory experiment procedures, which
are usually cumbersome and expensive, these miniaturized and automated
biochip devices offer a number of advantages such as higher sensitivity, lower
cost due to smaller sample and reagent volumes, higher levels of system inte-
gration, and less likelihood of human error.
A popular class of microfluidic biochips is based on continuous fluid flow
in permanently etched microchannels. These devices rely on either micro-
pumps and microvalves; or electrical methods such as electrokinetics, to
control continuous fluidic flow [4,5]. Some recent continuous-flow biochip
products include the Topaz™ system for protein crystallization from
Fluidigm Corporation, the LabChip system from Caliper Life Sciences, and
the LabCD™ system from Tecan Systems [6-8].
An alternative category of microfluidic biochips relies on “digital micro-
fluidics,” which is based on the principle of electrowetting-on-dielectric [9-12].
Since discrete droplets of nanoliter volumes can be manipulated using a pat-
terned array of electrodes, miniaturized bioassay protocols (in terms of liquid
volumes and assay times) can be mapped and executed on a microfluidic
chip. Therefore, digital microfluidic biochips require only nanoliter volumes
of samples and reagents. They offer continuous sampling and analysis capa-
bilities for online and real-time chemical or biological sensing [13]. These
systems also have a desirable property referred to as
dynamic reconfigurability,
,
whereby microfluidic modules can be relocated to other places on the elec-
trode array, without affecting functionality, during the concurrent execution
of a set of bioassays. Reconfigurability enables microfluidic biochips to be
“adaptive” to a wide variety of applications. System reconfiguration can also
be used to bypass faulty cells to enable microfluidic arrays to provide reliable
assay outcomes in the presence of defects.
Recent years have seen growing interest in automated chip design and opti-
mized mapping of multiple bioassays for concurrent execution on a digital
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