Biomedical Engineering Reference
In-Depth Information
approach has been successfully applied to cellular analyses [64-69]. The promise is
that DEP methods may be more sensitive than current approaches for the detection of
changes in cellular viability or obtain informative signatures at earlier stages of
commitment to cell death [70]. Cell separation can also be achieved by isodielectric
separation (IDS), for sorting cells based on electrically distinguishable phenotypes.
IDS involves separating cells and particles in an electrical conductivity gradient using
dielectrophoresis and can be applied in a continuous-flow device and is label free [71,
73]. Cell separation by differential mobility cytometry (DMC) provides a unique
separation approach employing oscillating flow and differential imaging to analyze
cells as they retard and adhere to an affinity surface such as a capture antibody. DMC
has the advantages of high cell capture efficiency and the tracking of cell
adhesion [73].
2.4 ADVANCES IN PLATFORM FORMATS: MICROFLOW
AND NEW LIGHT SOURCES
The prospects for the application of nanotechnology in healthcare and for the
development of personalized medicine appear to be bright [74-76] although in
the case of cellular analyses there are clear problems in cell handing that require
microscale solutions.
2.4.1 Microflow Cytometry
Miniaturization of cytometers for main laboratory-based activities is not of high value
if it merely repeats the performance envelope of already compact instruments.
However, advances in microfluidics bring new physical principles to bear at the
microscale that can have a real impact on the types of analyses. Measuring the DNA
content of eukaryotic cells is a fundamental task in biology and medicine. The
changes in capacitance generated by passing individual cells across a 1 kHz electric
field can be used to detect differences in DNA content of eukaryotic cells, leading to
the development of microfluidic “capacitance cytometry” [77].
Microfabrication also lends itself to production advantages and the possibility of
assays being configured by the design of a given microfluidic chip. Recent advances
in miniaturized microfluidic flow cytometry for clinical use have been described [78]
and there are numerous options for photonically coupling chips for fluorescence
event detection. Recent developments in microflow cytometry have involved focus-
ing the particles to be analyzed in the microfluidic channel, miniaturization of the
fluid handling components, miniaturization of the optics, and integration and
applications development. Strategies for focusing particles in a narrow path as they
pass through the detection region include the use of focusing fluids, nozzles, and
dielectrophoresis [79], as described above, but must deal with the microscale
fabrication issues. An example of the microfabrication solution to control fluid flow
in such systems is the recent development of groove-generated sheath flow directing
sheath fluid from the sides to the top and bottom of the channel, completely
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