K. Grenier
, D. Dubuc
, M. Kumemura
, H. Toshiyoshi
and H. Fujita
Institue of Industrial Science, The Univ. of Tokyo, 4-4-1 Komaba, Meguro-ku, Tokyo, Japan
Keywords: Coplanar waveguides, Permittivity, Biomedical transducers, DNA, Sensor, Microwave, Biology.
Abstract: This paper presents a biosensor, which both takes benefits from RF/microwave detection scheme for
contactless ability and from microtechnologies fabrication potentialities for massive integration of sensors
into lab on chip. The proposed sensor is based on transmission line (which is the basis element of numerous
microwave circuits) associated with a biological micro volume in interaction with electrical microwave
fields. Thanks to the transmission characteristic of the line, we then detect the presence of DNA inside its
nominal liquid environment with a measured sensitivity compatible with RF/microwave measurements
capabilities. The results then demonstrated the potentialities of this approach for the analysis of biological
parameters of ‘in vitro’ biological substance using microsystem integration facilities.
In the past decades, the biological and medical fields
have been strongly modified with the emergence of
various bio and micro-sensors for the
characterization and quantification of biomolecules.
Such sensors permit indeed to reach important
parameters for biologists. Classical detection sensors
(Bashir, 2004) are very effective, but may
sometimes suffer from limitations such as the use of
markers, that may modify the studied biological
substance. They may also imply high cost and
volumic equipments especially with fluorescence, as
well as low sensitivity.
To overcome these drawbacks, the use of
electromagnetic field as transduction in the bio-
sensor may present great advantages. It could
provide a non-invasive detection as it is contact less
in a biological environment, as well as label free.
Some studies have already been performed, notably
for toxicology purpose, with the work of Sebastian,
2004 in order to be able to detect heavy metal
pollutants in tissues. Some others have focused on
the RF field effects on human or livings cells for
dosimetry aims (Gabriel, 1996 for example).
In RF measurements, large volume of liquids are
usually involved during the characterization to
achieve a high sensitivity (Liu, 2008). Thanks to the
integration capabilities of microtechnologies, we
demonstrate simultaneously high sensitivity (for
DNA detection notably) and high compactness,
which is compatible with future massive parallel
Consequently, this paper deals with a very compact
RF based bio-sensor, which can serve to detect,
identify and quantify very low volumes (few μl) of
biological substances. As an example, DNA solution
has been chosen as detected solution in order to
prove our RF biosensor concept.
Figure 1: Schematic view of the proposed RF biosensor.
The second part of this publication presents the
architecture of our proof of concept demonstrator
and describes the validation of the measurement and
modeling procedure specifically developed for liquid
parameters analysis. The third paragraph deals with
the experimental protocol used and measurements
obtained for DNA detection inside buffer liquid
which highlight the potentialities of our RF/
Grenier K., Dubuc D., Kumemura M., Toshiyoshi H. and Fujita H. (2009).
In Proceedings of the International Conference on Biomedical Electronics and Devices, pages 398-401
DOI: 10.5220/0001547603980401
microwave based sensor for biological parameters
analysis as summarized in the conclusion.
2.1 Device Topology
The investigated RF biosensor is presented in Figure
1. It is composed of a RF transmission line with
polymer walls realized on top, in order to delimitate
the liquid biological substance area.
A coplanar type of line (a signal path localized
between two ground planes) has been chosen, as it
permits to elaborate all signal and ground planes on
the same surface in one technological step.
Thanks to the polymer walls realized on top of the
line, it is possible to characterize various biological
substances in an appropriate environment and with
very small volume (few μl range). The liquid is
inserted on top of the signal thanks to a micropipette
and well delimited with the polymer walls.
Figure 2: Electrostatic field distribution.
The principle of this biosensor is as follows: the
electromagnetic field propagates along the coplanar
line. The operating microwave frequency range
permits to assure a complete penetration of the field
into the biological substance, then enhancing the
sensitivity. The fluid presence translates into a
modification of the magnitude and phase of the
signal as the fluid presents different dielectric
characteristics than air. This electrical signature is
related to the biological substance properties, and
then permits its characterization/
The RF biosensor is consequently totally contact
less, which avoids any contamination of the
chemicals. Labels on the biomolecules are also
useless in this case.
Because of the coplanar topology of the line, the
electrical field is in consequence almost equally
distributed on both side of the line: in the substrate
and in the fluid. This phenomenon can easily be
noticed in Figure 2.
This permits to get a volumic interaction with the
biological substance and furthermore to enhance the
sensitivity of detection.
2.2 Calibration Protocol and
Test structures have thus been realized. Gold lines
have been deposited on top of a quartz substrate.
Polymer walls have then been performed on top to
elaborate the fluidic pool. The picture of the
obtained demonstrator is indicated in Figure 3.
Figure 3: Picture of the RF biosensor with liquid between
the polymer walls.
In order to calibrate the extraction procedure of the
liquid parameters, we have measured the
performance of the proposed test structure with DI
water. The Figure 4 presents the extracted
permittivity of the DI water (continuous line) and
the predicted one (dots) based on the cole-cole
theory (Buchner, 1999) (Jiang, 2004). The predicted
effective permittivity is computed thanks :
to the equation 1, which considers that the
dielectric field is equally distributed in the
water (upper part of the coplanar line) and
the quartz material (lower part of the
coplanar line).
the classical cole-cole equation, described
by equation 2, where ε
, ε
and τ are
respectively the permittivity at low
frequency, the permittivity at high
frequency and the relaxation time.
1+ (
The measured relative permittivity is extracted
from the phase of the transmission parameter
measured from 100MHz up to 40GHz.
Figure 4: Measured and modeled relative effective
permittivity of the test structure.
The good agreement (error lower than 15%)
observed between our proposed test structure and the
associated extracted procedure with theoretical data
taken in the literature then validates our approach
over a very broad bandwidth from 100 MHz up to
This validation step then opens the door to the
RF and microwave spectroscopy of biological
substance given electrical parameters as presented in
the next paragraph.
Both biological experimental protocol and results
are presented in this paragraph.
3.1 Biological Experimental Protocol
In order to perform the RF measurements, two
solutions have been prepared and characterized. The
first one is directly ready and commercialized for
characterization: a λ-DNA solution, which DNA
concentration corresponds to 0,37μg/μl. As
reference, the buffer solution in which the λ-DNA is
localized was also fabricated.
Both liquids have then been tested on our RF
biosensor. A micropipette was used to well localize
the liquid in the dedicated area, as shown in Figure
Figure 5: Picture of the RF biosensor under test during
DNA solution incorporation with a micropipette.
This figure also presents the RF test setup: two
microwave coplanar probes connected to an network
analyzer (which operates from 100MHz up to
40GHz) by cables.
We would like to emphasize the fact that our
concept is fully compatible with the use of micro-
3.2 Discussions
The electrical parameter, which is monitored,
corresponds to the phase of the transmission
parameter of the coplanar line. As already reported
in this publication, this parameter is related to the
permittivity of the biological substance and then to
its intrinsic constitution.
Figure 6: Phase of the transmission parameter vs
frequency for the two biological substances: buffer
solution w/ (line with circle marks) and w/o (line with
square marks) λ-DNA.
BIODEVICES 2009 - International Conference on Biomedical Electronics and Devices
The Figure 6 presents the measured phase of the
transmission parameters of the tested structure for
two cases: (1) when the line is covered with the
buffer only (line with square marks) and (2) when
the line is covered with DNAs inside the buffer (line
with circle marks). As the electrical properties of the
DNA molecule differ from the buffer one, we can
observe on the RF/microwave measurement the
signature of the DNA’s loading. We indeed obtain a
phase difference of 6° and 10° at 20GHz and 40GHz
respectively between the two cases, with and
without DNA, as summarized in the table I.
Table 1: Phase measurements summary.
Phase of the transmission
parameter in °
20 GHz 40 GHz
Without DNA -97 -153
With DNA -103 -163
Difference 6 10
The observed phase difference, around 7% in our
case, is larger than the minimum detectable phase
shift that we have estimated around 1°, but also
sufficiently high to envision microwave circuits with
enhanced sensitivity (7% multiply by the order of
the electrical function) like filter with operation
frequency sensitive to DNA concentration.
We also would like to outline that the use of
higher frequency increases the electrical signature
(the phase shift in our study) of DNA concentration,
and then to highlight one key point of our work,
which targets the integration of microwave (1-
30GHz) and even millimeterwave (30GHz to
110GHz or even higher) circuit for biological
This publication presents a proof of concept
demonstrator that emphasizes the potentialities of
RF/microwave detection and quantification of DNA
in its nominal biological environment. We take
benefit from the RF/microwave fields to achieve a
contact less detection scheme opening the door to ‘in
vitro’ analysis. We have first calibrated/validated
our RF sensor, and associated parameters extraction
procedure, with known liquid (D.I. water). We have
then detected the presence of DNA inside on host
liquid with a sensitivity, which is compatible with
measurement capabilities and future circuit design of
dedicated function.
Besides this electrical characterization, we
would like to outline that the fabrication of our
sensor is fully compatible with microtechnologies
and then inherit of their great interest, notably the
possible integration into lab-on-chip.
Furthermore, we think that it will be possible to have
access to the intrinsic DNA electrical parameters and
density, opening the door to the
quantification/discrimination of DNA inside its
biological environment.
Bashir, R., 2004. Advanced Drug Delivery Reviews, 56
Buchner, R., Barthel, J., Stauber, J., 1999. Chemical
Physics Letters 306, 57-63
Gabriel, S., Lau, R. W., Gabriel, C., 1996. Phys. Med.
Biol. 41, 2251-2269
Jiang, J. H., Wu, D. L., 2004. Atmos. Sci. Let. 5: 146-151
Khan, U., & al., 2007. IEEE Int. Microwave Symp., June
Liu, C., Pu, Y., 2008. IEEE Microwave and Wireless
Components Letters, Vol. 18, n°4, April
Sebastian, 2004. IEEE European Microwave Conference