Biomedical Engineering Reference
In-Depth Information
2.2.1 History of the Development of the Technique
Dielectric spectroscopy is based on impedance, as highlighted in Chap. 1, and is
used extensively in different fields, such as electronic engineering and chemistry.
The first publication relating to biological applications reported the use of radio-
frequency impendence to measure viable biomass [
40
]. Since its origin in the
biotechnology area, the technique has gained in importance, particularly since the
PAT initiative, as shown in a recent review [
41
].
2.2.2 Dielectric Spectroscopy in the Scope of the PAT Initiative
Process analysers are an important part of the PAT initiative [
42
], and they should
provide real-time process-related information, if possible of multivariate nature,
through non-destructive, non-invasive measurements. Currently, commercially
available dielectric spectrometers are built to withstand cleaning-in-place (CIP)
and sterilisation-in-place (SIP) while allowing in situ monitoring to provide real-
time information through high-frequency measurements. Most available devices
are highly customized and include a wide range of approved filtering and data pre-
processing techniques. The instruments are versatile and applicable to all types of
cells. On the other hand, capacitance measurements show dependence on tem-
perature, pressure, mixing rate, aeration rate, reactor volume, probe position and
proximity to metal components. However, the signal is reasonably stable if all the
above-mentioned parameters are kept as constant as possible [
43
]. The validity and
reliability of the gathered process information is highly dependent on correlation
to off-line measurements, as discussed later. Despite the advantages of dielectric
spectroscopy as a process analyser, its application is concentrated in the academic
field rather than in industry, with the exception of brewing [
44
-
48
].
The evolution of the application of dielectric spectroscopy over time, the
importance of data processing and the range of cell densities measured are sum-
marized in Tables
2
and
3
. ''Application'' refers to the cell type and cell line used,
as well as to the culture conditions and experimental set-up. ''Settings'' summa-
rizes, as far as the information available, the frequency settings used, the ranges
scanned and the interval for acquiring data applied.
Dielectric spectroscopy finds its application in fields such as molecular biology,
monitoring of transfection efficiency [
72
,
73
], protein folding [
74
] and food
technology [
75
]. Alternative but related methods include dielectrophoresis [
60
,
76
]
and electrochemical impedance spectroscopy [
77
].
Early work in dielectric spectroscopy was mostly concerned with improving the
instrumentation and the mathematical translation of the signal [
45
,
47
-
50
,
78
]as
well as exploration of the dielectric properties of cells [
79
,
80
]. A series of papers
was dedicated to exploring the frequency dependence of the capacitance mea-
surements and the appropriate techniques to extract meaningful information from
the obtained data [
44
,
45
,
81
,
82
]. Several types of corrections for changes in the
conductivity of the medium were proposed, and the most appropriate ones are now
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