Biomedical Engineering Reference
In-Depth Information
smartphones is an attractive prospect to the field of POC diagnostics. This
approach would involve using the existing camera and CPU of the mobile phone to
acquire an image of a sample, which can then be transmitted wirelessly to a remote
location such as a hospital or clinic. The Ozcan group have demonstrated a lens-
free microscope that can be installed on a mobile phone and is capable of imaging
red blood cells, white blood cells, platelets, and a waterborne parasite (Giardia
lamblia)[
107
]. Here the sample is loaded into the device attached to the back of
the smartphone (Fig.
13
a) and illuminated using an LED light source. The camera
sensor records a holographic shadow cast by the sample, which is then processed
by the CPU of the phone to reconstruct the image. This method does not require
bulky lasers or optical parts, making it lightweight and compact. More recently,
the same group reported fluorescence microscopy on a mobile phone [
127
]
(Fig.
13
b).
Label-free. There is an increasing interest in label-free sensing technologies
that can be implemented with microfluidic systems. In the contexts of molecular
diagnostics, there are several advantages to using label-free detection. These
include the reduced time and cost of preparing the sample, and the possibility of
detecting target molecules that cannot be labelled. We will now discuss three
label-free detection options that can be combined with microfluidic systems: SPR,
interferometry and electrochemical detection.
SPR is the most commonly used label-free detection method used in micro-
fluidic platforms [
121
]. In this approach, the light of a specific incident angle and
wavelength is used to excite surface plasmons in a thin film of metal. The eva-
nescent wave produced is highly sensitive to refractive index changes at the metal-
liquid interface. Therefore, when a ligand binds to immobilised antibodies at the
surface, a change in the SPR angle is detected. There have been a great number of
SPR immunosensors developed since its introduction in the 1990 s [
95
]. Recently,
Estmer Nilsson et al. used a microfluidic reagent handling system in combination
with SPR for detecting influenza virus [
30
]. By immobilising recombinant HA
proteins on the dextran matrix of a sensor chip and using SRP, they were able to
increase the sensitivity (detection range 0.5-10 lg/ml) compared to the standard
method. SPR imaging or SPRi, in which the reflected light is recorded on a CCD
camera, can be used to detect molecular species in a microarray format. Krish-
namoorthy et al. recently showed that it was possible to selectively deliver samples
to a single row in a microarray using electrokinetic flow focusing and SPRi for
high-resolution detection [
53
]. This approach therefore offers label-free detection
of binding events in parallel.
Interferometric label-free measurements have also been demonstrated in
microfluidic channels. Here, a coherent light source is split into two beam paths
that are directed into the sample. Binding of the analyte is directed to the region
containing only one of the beams, causing a refractive index change and therefore
a difference in phase shift with respect the reference beam. This shift can then be
detected in a projected interference pattern. Ymeti et al. showed that a Young
interferometer configuration can be combined with a microfluidic immunoassay
[
124
]. Here, microchannels served as optical waveguides for the beams, which
