J. Uhlemann

Influence of artificial body fluids and medical sterilization procedures on chemical stability of Parylene C

Among materials suitable for flexible encapsulation poly-para-xylylene (Parylene C), often chosen as protective coating for biomedical devices and variety of anticorrosion applications due to its favorable chemical and biological resistance, high thermal stability, low water vapor absorption, permeability, high biocompatibility as well as excellent dielectric and mechanical properties, is one of the most promising. In spite of a wide use only few systematic studies on biological and chemical stability of Parylene C have been carried out. In this work the influence of autoclave, electron beam (e-beam), gamma, ethylene oxide (EtO) and H2O2-plasma sterilization procedures as well as influence of in-vitro dynamic loading with artificial blood plasma (ABP) and cerebrospinal fluid (ASCF) and 0.9 % NaCl on chemical resistance and crystallinity of Parylene C were studied by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The samples, treated with e-beam sterilization, show substantial changes in their chemical content comparing to the untreated state. The XPS-analysis revealed the intrusion of CH- and CN-groups into the polymer structure and formation of inorganic chlorides on the surface of Parylene C. The second effect was also present in the samples after EtO-treatment. No detectable changes in chemical content of polymer films were observed after gamma, plasma and autoclave procedures. The reduction of Cl-concentration in Parylene C, resulted from damaging of its structure, was found in all the samples loaded with fluids. Additionally, after the fluid influence, the already mentioned implantation of nitrogen and formation of inorganic chlorides have been observed. According to the XRD-results, the autoclave sterilization and fluidic treatments caused the significant ride of Parylene C crystallinity grade. Low crystallinity increase was detected after EtO and plasma procedures, while the both irradiation treatments leads to stronger marked amorphism of the studied structures.

Barrier properties of polymer encapsulation materials for implantable microsystems

Biocompatible polymers utilized for flexible encapsulations of implantable microsystems provide many advantages compared to widely used rigid titanium or ceramic packages. However, polymers alter their properties due to interactions with their environment. As a result the protective function of these materials especially for long-term implants is not reliable. Therefore, we investigated barrier properties against water vapor of silicone and Parylene C membranes. And we combined these polymers to a multi-layer membrane to enhance the protective function of such an encapsulation system. Applying a bonding agent between two polymer layers increases the strength of the sample as well as the barrier properties significantly.

3D-microfluidic reactor in LTCC

The study and verification of fluids and chemical reactions in the macroscopic range is widespread in the pharmacy, in the chemical engineering and in the medical and biotechnological industry. By transferring the reactor structures in microfluidic solutions the process parameters can be improved, analyses optimized as well as new ranges of applications opened. The preliminary works of our department show that the thick layer technology and especially the multilayer technology by means of Low Temperature Cofiring Ceramic (LTCC) offer a promising possibility for the miniaturizations of fluidic devices. The aim of this work was the conversion of parameter specifications from the chemical engineering in a first pattern construction of a LTCC microreactor. Thereby sensors for the measurement of the fluidic characteristics had to be integrated into this compound and their utilizability had to be proved.

Cytotoxicity of COB materials

The standards DIN EN ISO 10992 Part 1: 12-2003 and Part 5:11-1999 demand different tests for cytotoxicity including in vitro methods for evaluation materials in application of medical devices. Special features are materials for packaging processes in the field of medical micro devices. In this context the working group selected fundamental systems of materials and contact layers for testing in contact with the standard cell 3T3 clone A 31 and NCTC clone L929. One of the advanced methods includes a spectroscopic measurement of the metabolism. The results permit a gentle differentiation of materials cytotoxicity. Examples are shown in this paper.

Fluid Dynamic Load of Polymers Used as Encapsulation Material for Implantable Microsystems.

Biocompatible polymers utilized for flexible en- capsulations of implantable microsystems provide many ad- vantages compared to widely used rigid titanium or ceramic packages. However, polymers alter their properties due to interactions with their environment, but especially for long- term implants, a reliable protective function of these ma- terials is required. To investigate the protective function of different polymers, we developed an in vitro measuring setup which facilitates a fluid dynamic load of polymeric encapsulation materials. Measuring of polymer covered re- sistive and capacitive structures enables the characteriza- tion of the protective function.

Biostability issues of flash gold surfaces

Being chemically inert and non-toxic and having excellent electrical properties gold is known as one of the most suitable materials for fabrication of long-term implantable electronic devices. In spite of this fact, stability of structures with flash gold finish layers (electroless Ni @ immersion Au or electroless Ni @ electroless Pd @ immersion Au), widely used in electronics packaging, is questionable. Such layer configurations are often characterized as not sufficiently stable by applications in humid or corrosive environments and are poorly investigated under the influence of physiological factors as living tissues, microorganisms and body fluids. In this work biostability of FR4 @ 50 µm Cu @ 4 µm Ni @ 0.1 µm Au in simulated blood plasma was studied. The samples were stressed dynamically in a special circulation system, keeping the values of temperature, pressure and flow velocity similar to the natural parameters of a human body. The alterations in topography and structure integrity, chemical composition and wetting properties of the samples surfaces have been investigated by optical microscopy, atomic force microscopy (AFM), laser profilometry, contact angle measurements, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). Cracks formation and delamination of a gold layer, significant mass losses and precipitation of the foreign substances have been observed.

Researching of biochemical degradation of electronic materials in fluid electrolytic mediums

A human body environment has a very composite chemical temper, which includes cations of metals, anions of salts and organic acids. Degradable processes that arise in this medium between biological system and implanted metallic modules chosen as biomaterials by the reason of superior mechanical properties that allow them to be used in load-applications can be harmful and must be explained. The standards ISO 10993 Part 15:2000, Part 17: 2002 and Part 18: 2003 determinate test claims for identification and quantification of bound medical products from metals and alloys; a document of German Institute for Standardization DIN 50905 Part 2: 1987 gives a general guidance on methods of metals corrosion explorations and corrosion testing. Accordingly to these standards investigation of chemical stability of the selected materials (in this case System 1 consist of FR4 with layers of Cu (85 mum) -Ni (6-7mum) -Pd (0.25 mum) -Au (0.06 mum); System 2 consist of Al2O3 substrate with thick film AgPt; System 3 -a silicon wafer, phosphor doted, crystallographic orientation <1 0 0>, thickness 375 mum) under dynamic influence of 0.9% NaCl water solution, synthetic blood plasma (SBF -simulated body fluid) and simulate liquor cerebrospinalis fluid during assigned time in settled conditions have been carried out, processes of surface degradation and alteration have been analyzed.

Biostability of Electronic Packaging Materials

Biostability is concerned with the interactions take place between an integrated electronic system, restoring physiological functions often with a long time application and the components of the human body (tissues, fluids, gases, and applied medicaments). Organism with its specific inner conditions (temperature, pressure, pH-value, liquid flow rate, concentration and complex chemical compound) assures for systems constituents (conduct materials, allows, organic and inorganic semiconductor) a stressed medium which accelerates degradable processes (destruction, migration, dissolution, corrosion, delaminating, functions loss, structure alterations, etc.). These processes ? difficult interactions mostly on the boundary surface that stand in depending from the contact time. Our main goal is to consider the principles of these interactions, to study alterations through living organisms dynamic loading, to modulate a long time stability of packaging arrangement under bio-stress, to make dynamic measurements with packaging and housing materials and simulated body fluids (for example physiological sodium chloride water solution, synthetic plasma, simulate Liquor cerebrospinalis fluid), to definite quantitative und qualitative alterations of the fluid and materials surface, to rationalize a selection of biomaterials.

Packaging of electronic devices for long-term implantation

Development of smart medical devices for long-term implantation requires new encapsulation technologies with a special focus on flexible packaging of electronic devices. Biocompatible, high performance polymers seem to be suitable for such applications, however their protective function i.e. suppressing harmful interactions between the human and the foreign body is still unknown. Here, we evaluated this protective function of six polymers with regard to surface properties, water absorption and water solubility. Among all polymers investigated, silicone (low-consistency) showed the best characteristics compared to epoxy resin or polyurethane.

Characterization of ionic permeability and water vapor transmission rate of polymers used for implantable electronics

Biocompatible polymers used as encapsulation and packaging materials for implantable electronic devices have to comply with numerous requirements. Especially their barrier properties against water molecules and ions are of particular interest regarding the reliability of the encapsulation as well as functional integrity of the electronic components since water and ions on the circuit board may evoke corrosion, leakage current and finally the failure of the device. This paper describes a measurement setup to investigate the ionic permeability under in vitro conditions of polymeric membranes manufactured from various biocompatible polymers. Ionic permeability and water vapor transmission rate representing the barrier properties of these membranes were investigated. First results were obtained for polyimide, silicone, polyether ether ketone and polyamide, whereas polyimide evinced the best properties.