Biomedical Engineering Reference
In-Depth Information
Full working laboratories that perform molecular diagnostics use bench-top
systems such as PCR cyclers and separation columns that are simply impractical
for POC applications. To make them mobile, they therefore need be scaled down
but still retain the sensitivity and specificity of the industry standards.
Home care and developing world applications should require minimal or no
user training. In most cases, the person performing the test will have little or no
experience with medical diagnostics. Therefore, the test must be quick and simple
to perform so that it can be used at home or by a healthcare worker in the field.
Ideally, it would provide a basic yes/no result to avoid any user misinterpretation.
Economic factors also play an important role in choosing the next diagnostic
platform. Any portable device needs to be mass produced cheaply and require
minimal peripheral equipment. The operation of these devices must also be kept
low-cost by using small reagent volumes to pretreat and handle the samples. The
costs can be further reduced by isolating the peripheral components, such as readers
and temperature controls from the samples. This eliminates the need for cleaning
because the element containing the sample is simply disposed of after use.
Microfluidic systems have the potential to meet all of these needs and become
widely used in the field of diagnostics. The following section highlights some of
the more recent developments aiming to meet these requirements.
4 The Challenges in Molecular Diagnostics Being Met
by Microfluidic Technology
Pretreatment of the sample. Biological samples are a complex mix of many
different molecules. Before a sample can be analysed, it must first be pretreated to
separate the target analytes from the rest of the unwanted ones. In the case of
blood, the conventional laboratory solution is to use centrifugation to provide
purified plasma, but this can be a lengthy procedure and is also not feasible in
resource limited-settings. Therefore, microfluidic solutions have been developed in
order to perform on-chip sample preparation. These include capillary electro-
phoresis, dielectrophesis, liquid chromatography, optical and magnetic fields, fil-
tration by micro-structures, diffusion, and centrifugation. Several good reviews
exist that discuss the current state of microfluidic separation [
64
,
115
] and the
following will summarise some of the more recent developments.
The microfluidic H-filter, first developed in the 1990 s by [
10
], works by
exploiting the purely laminar flow within microchannels as shown in Fig.
3
a. As
smaller molecules diffuse faster than larger ones, they move across the width of the
channel and are therefore separated from the mixture at the outlets. Applications
include the extraction of small analytes from whole blood [
41
] and saliva[
43
].
Inertial forces within microchannels can be used to separate analytes from cells
in whole blood samples as demonstrated recently by Wang et al. [
110
]. Similarly
to lateral flow POC devices, the sample is first filtered using a paper film at the
inlet to remove up to 90% of the cells from the plasma. The cells and analytes
