CONTACT LESS RADIO-FREQUENCIES BIOSENSOR FOR

BIOLOGICAL PARAMETERS ANALYSIS

K. Grenier

, D. Dubuc

, M. Kumemura

, H. Toshiyoshi

and H. Fujita

LIMMS/CNRS-IIS,

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.

1 INTRODUCTION

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

analysis.

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/

398

Grenier K., Dubuc D., Kumemura M., Toshiyoshi H. and Fujita H. (2009).

CONTACT LESS RADIO-FREQUENCIES BIOSENSOR FOR BIOLOGICAL PARAMETERS ANALYSIS.

In Proceedings of the International Conference on Biomedical Electronics and Devices, pages 398-401

DOI: 10.5220/0001547603980401

 SciTePress

microwave based sensor for biological parameters

analysis as summarized in the conclusion.

2 RF BIOSENSOR DESCRIPTION

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/

identification/quantification.

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

Validation

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).

r,eff

r,quartz

r,Water

(1)

 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.

CONTACT LESS RADIO-FREQUENCIES BIOSENSOR FOR BIOLOGICAL PARAMETERS ANALYSIS

399

r,Water

∞

−

1+ (

)

(2)

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

40GHz.

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.

3 EXPERIMENTS

AND DISCUSSIONS

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-

channel.

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.

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400

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

analysis.

4 CONCLUSIONS

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.

REFERENCES

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

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