Biomedical Engineering Reference
In-Depth Information
1 Introduction
Microfluidic technologies have produced a broad range of applications for
chemistry and biology in the past 20 years, covering such topics as chemical
synthesis, separation of compounds, and analysis of biological samples, e.g. living
cells [ 25 , 46 , 98 , 112 ]. Integrated components for sample manipulation, separation
and detection on a single microfluidic chip have led to the terms 'micro total
analysis system' (lTAS) [ 49 , 63 ] and the more general 'lab-on-a-chip'. The first
decade of research saw the development of new materials and fabrication tech-
niques along with new detection methods. First applications focussed on the
downscaling of analytical methods and the use of microsystems for fluidic han-
dling, e.g. to deliver the sample to a sensor [ 74 , 96 ]. The first glass microfluidic
platforms were made for capillary electrophoresis (CE) and demonstrated
advanced separation efficiencies [ 17 , 120 ]. Later, microchips for DNA amplifi-
cation by polymerase chain reaction (PCR) were fabricated and showed promising
performance [ 50 , 52 , 119 ]. Microfluidic methods for DNA analysis [ 16 ] as well as
cell analysis [ 32 ] were then introduced. These proof-of-concept studies in the first
years raised the hope to revolutionise analytical chemistry and related fields,
including diagnostics. Advances and simplifications in the fabrication technology
of microfluidic chips, mainly driven by the use of cheap polymers such as
poly(dimethylsiloxane) (PDMS), have made the technology accessible to more
than just microsystems engineers. As a result, during the past few years, micro-
fluidics has found its way into many analytical, biological, and chemical labora-
tories. More recently, the technology has been successfully implemented in
chemical synthesis [ 94 ], cell studies [ 29 , 80 , 89 , 98 ], proteomics [ 1 , 26 ], phar-
macological screening [ 28 ], and point of care (POC) diagnostics [ 31 , 38 , 44 ].
Although there has yet to be the so-called 'killer' application that many hope
will lead to a global market for miniaturised systems [ 6 ], there have been a number
of high-impact publications in the field, often focussing on specific questions in
academic sciences [ 14 , 19 , 52 , 72 , 113 , 117 ]. However, microfluidic technology
has the potential to be used in routine diagnostic applications because it can
address and solve the many technological challenges. Figure 1 shows what an
idealised diagnostic device containing microfluidic technology might look like. In
this case, a sample would be placed on the disposable end, where it is pretreated
and directed to microfluidic channels. The target molecule(s) then would be
captured and the signal electronically recorded by a reusable section. Such a
device would offer high sensitivity within minutes from low volume samples, all at
low manufacturing costs.
In the following section, the major benefits of microfluidics are described. After
giving a brief summary of the needs for molecular diagnostic, including POC
devices, we present and discuss recent advances in microfluidic technology as well
as detection methods adapted for microfluidics that may be important for future
developments.
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