Biomedical Engineering Reference
In-Depth Information
The evanescent field can also be used for label-free detection, which is then based
merely on refraction. The penetration depth of the evanescent field is
typically only a few hundred nanometers; the refractive index of the medium
determines the propagation of the radiation. Hence, it is advantageous if large
analyte molecules have to be detected, such as proteins, as they lead to a higher
change in the refractive index. Furthermore, when the sensing layer is being
prepared, it has to be ensured that analyte binding occurs within the penetration
depth of the evanescent field, otherwise the binding cannot be detected by the
transducer and therefore will not be transformed into a quantifiable signal.
The best examined and most widespread evanescent field technique uses surface
plasmon resonance (SPR) on gold surfaces [
39
]. The respective systems have been
further developed continually [
40
], including related techniques, such as SPR
imaging [
41
] and localized SPR [
42
]. Other waveguiding methods make use of
grating couplers or prism couplers; the latter was introduced as a so-called
''resonant mirror'' [
43
]. Furthermore, evanescent field techniques have been
combined with interferometric principles, as realized in Mach-Zehnder and Young
interferometers [
39
,
44
,
45
]. Recently developed evanescent field techniques for
label-free optical detection for biosensors include use of Bragg gratings, photonic
crystals, and optical ring resonators [
44
,
45
].
Apart from refractometry, label-free optical detection can also employ reflec-
tometry. In this case, signal response changes result from changes in the optical
thickness, i.e., the product of the refractive index and the physical thickness, where
changes of the latter prevail. Hence, the evanescent field does not have an impact
here, and binding events do not necessarily have to be near the surface [
39
]. Again,
large molecules are preferred for detection as they lead to greater thickness
changes. Detection methods using reflectometry include ellipsometry, which is
based on polarized light, and reflectometric interference spectroscopy, which can
be performed with white light, which is why reflectometric interference spec-
troscopy may be considered as a simplified version of ellipsometry [
46
].
In addition to the numerous optical detectors which are already available,
ongoing research is motivated by the aim of introducing new label-free transduction
principles for biosensors that allow, in particular, the label-free detection of low
concentrations or small molecules or both. Currently under investigation are,
e.g., terahertz spectroscopy [
47
] and surface-enhanced Raman spectroscopy [
48
].
2.1.4 Acoustic Transduction Principles
Gravimetric (mass-sensitive) transduction principles use mechanical acoustic
waves which are typically generated by means of piezoelectric materials. Signal
response changes mainly result from mass changes in the biorecognition layer;
hence, it is advantageous if large molecules have to be detected [
49
,
50
]. Acoustic
detection is usually label-free, but the use of nanoparticles as mass labels to
increase mass sensitivity has been reported [
51
].
