Chemistry Reference
In-Depth Information
Academic institutions and corporations have developed a plethora of lab-on-a-chip devices for different
applications; however, the overwhelming need is for a universal application that could trigger widespread use
of microchips in biomedicine. There is a general consensus that miniaturization should have advanced more
quickly than it has. A few years ago, many analytical chemists were enthusiastic about chip-based analyses,
but one can now sense disappointment and disillusionment among the members of that community. If there
is no widely used application, the development of microfluidic devices will not be economically profitable.
This phenomenon is known as the absence of a 'killer' application. The term
… is commonly used to describe a product which has such highly desirable properties that it generates very large
revenues with attractive margins in a comparatively short amount of time. In addition to this purely economic
description it also helps to promote the underlying technology, thus helping typically 'disruptive technologies' (a
technology that enables products which dramatically change markets due to their (often unexpected) performance
and which are not achievable by simple linear extrapolation of existing products or technologies
' [50]
Examples of killer applications are digital photography and flat panel television screens. Let us hope that a
killer application will soon be found, that the 'world-to-chip' problem will be solved as quickly as possible,
and that obstacles to developing the ultimate method of green analysis will be surmounted. Interestingly, the
development of LOC systems can be described by a 'hype cycle' model introduced in 1995. According to
Mukhopadhyay [51], the model has five stages: a technology trigger, a peak of inflated expectations, a trough
of disillusionment, a slope of enlightenment, and finally, a plateau of productivity. He believes that
microfluidics is now on the slope of enlightenment. Many microfluidics proofs-of-concepts have been
advanced, but the gap between academic proofs-of-concept and the need of industry is wide. Only 1
of
proofs-of-concept become commercialized [51] and most innovative technologies take longer than anticipated
to develop large markets.
%
9.2.5
Gradient elution moving boundary electrophoresis and electrophoretic exclusion
Despite the stagnation of the development of CE instrumentation, some exciting proposals are still coming
forward. A mode of CE called gradient elution moving boundary electrophoresis (GEMBE) is a further step
in the direction of making CE technology portable and minimizing sample preparation. GEMBE was
developed by Ross
et al.
of the US NIST Biochemical Science Division [52-54]. GEMBE operates by
pumping a buffer solution under controlled pressure into the sample vessel in the opposite direction of the
rapidly moving analytes. The opposing buffer flow acts as a fluid gate between the sample reservoir and the
capillary. The pressure is gradually reduced during the analysis runtime and a specific analyte is detected
when the flow becomes sufficiently weak that the electrophoretic migration of the analyte pushes it against
the pressure flow into the capillary. GEMBE can analyse samples in complex matrices, such as whole milk,
blood serum and dirt in solution. Usually, samples in complex matrices are difficult to analyse because the
heavy components (e.g. fat globules in milk, proteins in blood or particulates in environmental samples) can
foul the separation capillary. In the case of GEMBE, this does not happen because the pressure flow keeps
out the unwanted material during analysis and the various analytes enter the channel at different times based
on their particular electrophoretic motion.
The analytes are detected by contactless conductivity. The detector signal is in the form of steps, because
the conductivity of the capillary at the detection point changes when a new analyte band enters the detector
window. Those steps can be differentiated to create peaks on an electropherogram. However, detection can be
simplified even further. Because the separation channel is so short, only one moving boundary step is present
in the channel at any given time, and the current through the channel can be measured and used to send a
signal comparable to that which is normally generated by more complicated means of detection (see Figure 9.6).
