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Procedia Engineering 120 (2015) 45 48

EUROSENSORS 2015

Plasma Nanofilms as
Biocompatible and Antibacterial Interface for In-Vivo Sensors
M. Bergmann*, L. Ledernez, G. Urban
Laboratory for Sensors, Department of Microsystems Engineering, Albert-LudwigsUniversity of Freiburg, Georges-Khler-Allee 103 79110, Freiburg,
Germany

Abstract

In this work the magnetron enhanced plasma polymerization was used to produce bio-hemocompatible surface
coatings. Their physical and chemical properties as well as their behavior in biological environment in-vivo and invitro were investigated. By the precise detection of the protein adsorption, one could devise the best process
parameters. The implantation of a coated sensor dummy proved a highly biocompatible respectively bioinert
coating. This type of coating drastically increases the functionality and efficiency of many medical implants and invivo sensors.

by Elsevier
Ltd. This
an open access
2015
2015Published
The Authors.
Published
byisElsevier
Ltd. article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Peer-review
under
responsibility
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organizing
committee of EUROSENSORS 2015.
Peer-review under responsibility of the organizing committee of EUROSENSORS 2015

Keywords: biocompatibility, hemocompatibility, plasma nanofilm, plasma polymerization, bioinert

* Corresponding author. Dr.-Ing. Michael Bergmann, Laboratory for Sensors, Department of Microsystems Engineering, Albert-LudwigsUniversity of Freiburg, Georges-Khler-Allee 103, 79110, Freiburg, Germany
E-mail address: michael.bergmann@imtek.de.

1877-7058 2015 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Peer-review under responsibility of the organizing committee of EUROSENSORS 2015

doi:10.1016/j.proeng.2015.08.562

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M. Bergmann et al. / Procedia Engineering 120 (2015) 45 48

1. Introduction
In the development of biocompatible materials for biomedical applications and biosensors, the foreign body
response is an important issue [1][3]. The healing of tissue surrounding the device often interferes with its function.
Events like protein deposition, hemostasis, inflammation, tissue repair, infections and the encapsulation of the
functional part of the sensor for example are the main cause of failure of the implanted device [4]. In this study
biocompatible nanofilms are produced by means of a plasma polymerization process using a low-pressure
magnetron-enhanced 15 kHz glow discharge. This process allows the precise adaption of the surface properties to
ensure a biocompatible and antibacterial interface.
2. Experimental Section and Discussion
2.1 Plasma Polymerization
A magnetron enhanced plasma polymerization process was
conducted in a system from the company Shinko Seiki. This comprises
two parallel titanium electrodes with a distance of 10 cm. In between the
samples rotate on a wheel at floating potential. The circular movement
of the samples ensures a good homogeneity of the resulting plasma
nanofilms. Circularly arranged magnets behind the electrodes
concentrate the plasma between the electrodes. This concentration leads
to a higher efficiency as well as a better thickness homogeneity. Before
every coating the plasma chamber is evacuated down to a pressure of
0.1 Pa to eliminate the possibility of cross contamination.
Afterwards, the process is run at a pressure of 5 Pa. A mixture of
methane and oxygen was used as starting material. Depending on the
mixture of these gases different amount of oxygen was embedded into
the film. Subsequently, different surface properties could be achieved.
The different recipes are listed in Table 1. Further information can be
found elesewhere [5], [6].

Table 1: process parameters.used for the different model surfaces to be analyzed

recipe
[number]
I
II
III
IV

gases and flowrates

[sccm]
2.5 CH4 + 1.3 O2
2.8 CH4 + 1.1 O2
3.0 CH4 + 1.0 O2
5.0 CH4

growth rate
[nm/min]
0.2
0.9
1.2
2.0

Figure 1: Commercial plasma polymerization

equipment from Shinko Seiki

power
[W]
45
45
45
45

2.2 Physical and Chemical Characterization of the Plasma Nanofilms

The plasma nanofilms were investigated using different surface analytical methods such as x-ray photoelectron
spectroscopy (XPS) and water contact angle (WCA).

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M. Bergmann et al. / Procedia Engineering 120 (2015) 45 48

Table 2: Composition of the different nanofilms analysed by XPS and a take-off angle of 45

Coating recipe
[number]
I
II
III
IV

C percentage in
the nanofilm
[%]
65
71
72
89

O percentage in
the nanofilm
[%]
31
26
25
9

A higher amount of polar groups was embedded into

the film [Table 2] when more oxygen was used in the
precursor gas mix; this correlates well with the
decreased water contact angle [Fig. 2]. The
embedding of more oxygen and therefore more polar
groups into the nanofilm leads to a decreasing
dynamic water contact angle and the contact angle
nearly can be tuned continuously. Also the aging of
these nanofilms was investigated using this
measurement technique. One noticed a very low aging
when keeping the samples in a solution such as
deionized water.

dynamic contact angle []

X-ray photoelectron spectroscopy and dynamic contact angle measurements were performed to gain information
about the chemical/physical properties of the plasma coatings and are correlated to the behavior of those surfaces in
biological systems.
90
80
70
60
50
40
30
20
10
0
I

II

III

IV

Coating recipe
Figure 2: dynamic advancing contact angle of different coating
receipts measured on silicon wafers

2.3 Biological Characterization of the Plasma Nanofilms

fibrinogen (g/cm^2)

Beyond the different surface analytical methods,

1,6
the in-vitro interaction with different biological
sample materials was also tested. As it is known from
1,4
the foreign body response, one can notice that proteins
1,2
are usually the first constituents arriving on a foreign
1
surface implanted in to the human body. Therefore it
0,8
is important to investigate this initial event, which
0,6
determines the following events such as
0,4
encapsulation. This was done in-vitro by quartz crystal
0,2
microbalance measurements to detect the adsorbed
0
amounts of proteins [Figure 3]. From these results it
I
II
III
IV
Au
PS
could be deduced that the amount of adsorbed proteins
surface
on the interface also correlates with the coating recipe.
The adsorption of proteins could be tailored from a high Figure 3: Adsorbed amount of the protein fibrinogen in respect to the
deposition compared to a bare gold surface to a very low nanofilm coating referenced to a bare gold surface which is assumed
deposition on recipe I. Using the molar weight of the already as very biocompatible
proteins and the maximum coverage of proteins on the
surface, one can deduce a very native structure of adsorbed proteins on the surface. This was confirmed by
measurements using Fourier transform infrared spectroscopy (FTIR) measuring a comparable protein structure on
recipe I as native protein in buffer solution. [5]

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M. Bergmann et al. / Procedia Engineering 120 (2015) 45 48

Considering these promising in-vitro results, sensor

dummies were implanted into a swine for 6 month. The
place of implantation was the superior vena cava. The
substrate material was titanium. After the implantation it
could be seen that the sample was kept completely free
of any encapsulation on the coated part whereas the
uncoated part of the sensor was completely encapsulated
by a collagen bag.
4. Conclusion

# E Coli

The antibacterial behavior of the coating was tested using E. coli GFP. Different types of materials were coated and
examined, including polystyrene, polymethylmethacrylat (PMMA), glass and silicon. These samples were inspected
after 24 h via fluorescent microscopy. Figure 4 shows the immense reduction of attached bacteria.
This study clearly shows the antibacterial behavior of
E C oli on substrate
10000
E C oli on C V D
the plasma coating. Reduction in bacteria adhesion of up
to 99 % could be reached, regarding the first
1000
colonizers.
100
10
1
polystyrene

silicon

PMMA

glass

Figure 4: average counted number of bacteria detected on the surface of

different types of materials, a reduction of up to 99% could be achieved

The flexibility of the coating process allows the tailoring of the substrate/surrounding interface. The implantation of
polar groups like oxygen can be tuned continuously. Especially for biosensors this coating provides an opportunity
to enhance the biocompatibility without disturbing the inherent functionality of the sensors.
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B. D. Ratner, The biocompatibility manifesto: biocompatibility for the twenty-first century., J. Cardiovasc. Transl. Res., vol. 4, no. 5,
pp. 523527, Oct. 2011.

[4]

R. Turner, D. Harrison, R. Rajotte, and H. Baltes, A Biocompatible Enzyme Electrode for Continuous in ho in Whole Blood, Sensors
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[5]

M. Bergmann, Oberflchenmodifikation mithilfe der magnetfelduntersttzten Plasmapolymerisation, AlbertLudwigsUniversitt

Freiburg im Breisgau, 2015.

[6]

L. Ledernez, Investigation of a Magnetron Enhanced AF Plasma Polymerisation Process for Sensor Coating, 2011.