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Biocompatible Hermetic Encapsulation for Implantable Miniaturized Biomedical Sensor System
Available online at www.sciencedirect.com
ScienceDirect Procedia Technology 27 (2017) 42 – 43
Biosensors 2016
Biocompatible hermetic encapsulation for implantable miniaturized biomedical sensor system C. Jorsch a*, M. Guenther a, G. Gerlach a a
Solid-State Electronics Laboratory, Technische Universität Dresden, 01069 Dresden, Germany
Abstract The field of medical engineering with high standards for implantable applications requires frequently not only sensitive measuring systems but also long term stability and less inflammatory reactions after implantation. Implantable electronics relies on a hermetic and dissolvent consistent encapsulation. Already used materials, such as parylene C, have excellent barrier properties, protect from corrosion and show good bio-stability. But, the biocompatibility of such materials is often insufficient. The in this work described encapsulation with a special coating of polyethylene glycolated amino acids could improve this. The better cell compatibility as well as the protein repellent behaviour and the changes in surface characteristics implies that this coating enhances the functionality and biocompatibility in general. This encapsulation is of current interest for an implantable blood glucose measuring system based on the piezoresistive pressure sensor chip containing a glucose-sensitive hydrogel in its cavity. © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license © 2016 The Authors. Published by Elsevier Ltd. (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-reviewunder underresponsibility responsibility organizing committee of Biosensors Peer-review of of thethe organizing committee of Biosensors 20162016. Keywords: biocompatible encapsulation, parylene C, amphiphilic block copolymers
1. Main text The treatment of metabolic diseases, such as diabetes mellitus, needs especially a simultaneous and continuous monitoring of the different metabolism-related parameters (blood glucose level, pH value and carbon dioxide partial pressure). In this regard, new and mainly rewarding sensor arrays based on a hydrogel swelling attract the main
* Corresponding author. Tel.: +49 351 463 43798; fax: +49 351 463 32320. E-mail address: [email protected]
2212-0173 © 2017 The Authors. 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 Biosensors 2016 doi:10.1016/j.protcy.2017.04.020
C. Jorsch et al. / Procedia Technology 27 (2017) 42 – 43
interest for the on-line applications in the medical diagnostics. Therefore, the efforts in this work were made to improve a miniaturized implantable sensor array microsystem consisting of several hydrogel-based sensors. The working principle of the sensors as well as the type of the stimuli-responsive hydrogel depends on the applications, such as temperature sensor, pH sensor, glucose sensor and more. [1, 2] Each of them has an integrated piezoresistive Wheatstone bridge at the surface of the flexure plate which acts as mechano-electrical transducer for the transformation of the plate deflection into an electrical output voltage Vout. [3] The stimuli-responsive hydrogel swells and deflects the bending plate. The whole sensor system is featured with a biocompatible encapsulation needed for the device implantation into the human body. A multi-layer sensor encapsulation consisting of parylene C and amphiphilic block-copolymers (Fig. 1b) was proposed for subcutaneous implants and characterized using contact angle measurements (Fig. 1a), atomic force microscopy and X-ray photoelectron spectroscopy. The coupling of these polymers to mostly inert parylene C was successfully performed by means of the developed coating procedure. With the coupling of different polymers, the change of surface characteristics was observed. Biocompatibility studies with human fibroblast cells were performed to indicate cell-based reactions referable to the future implant material. Figure 1c shows for block-copolymer samples just 20 % less cell viability, while the decrease on parylene C surface is around 40%. In order to understand the behaviour of implants at physiological conditions, the interaction of the implant surface with biological objects like proteins, serum and blood plasma is discussed taking into account a possible protein adsorption on the implant surface due to the tissue inflammation around the implant, which should be minimized.
Fig. 1. (a) Contact angle measurements with water on parylene C, θ = 90.0 ° (left) and on parylene C/amphiphilic block copolymer, θ = 44.3 ° (right); (b) Structural formula of the block copolymer PEG114-b-p(L-Glu)40-b-p(L-Leu)10; (c) Fluorescence intensity (Cell Titer Blue Assay) as an indicator for the cell viability after the direct incubation on the coated biomaterials (n=6).
The biocompatibility of implant-material plays a major role in design and development of implantable devices. Biocompatibility studies performed in this work showed that the proposed surface modification is useful for all types of implants. Acknowledgements The authors thank the Deutsche Forschungsgemeinschaft (DFG) fort the financial support (RTG 1865 “Hydrogel based microsystems”). References [1] Gerlach, G. and Arndt, K.-F. (Hg.): Hydrogel Sensors and Actuators. Engineering and Technology. Berlin, Heidelberg: Springer-Verlag, 2009 [2] Lin, G.; Chang, S.; Hao, H.; Tathireddy, P.; Orthner, M.; Magda, J.; Solzbacher, F.: Osmotic swelling pressure response of smart hydrogels suitable for chronically implantable glucose sensors. Sensors and Actuators B: Chemical 144 (1), 332–336, 2010. [3] Guenther M., Wallmersperger T., Gerlach G.: Piezoresistive chemical sensors based on functionalized hydrogels, Chemosensors, 2(2) 145170. 2014.
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ScienceDirect Procedia Technology 27 (2017) 42 – 43
Biosensors 2016
Biocompatible hermetic encapsulation for implantable miniaturized biomedical sensor system C. Jorsch a*, M. Guenther a, G. Gerlach a a
Solid-State Electronics Laboratory, Technische Universität Dresden, 01069 Dresden, Germany
Abstract The field of medical engineering with high standards for implantable applications requires frequently not only sensitive measuring systems but also long term stability and less inflammatory reactions after implantation. Implantable electronics relies on a hermetic and dissolvent consistent encapsulation. Already used materials, such as parylene C, have excellent barrier properties, protect from corrosion and show good bio-stability. But, the biocompatibility of such materials is often insufficient. The in this work described encapsulation with a special coating of polyethylene glycolated amino acids could improve this. The better cell compatibility as well as the protein repellent behaviour and the changes in surface characteristics implies that this coating enhances the functionality and biocompatibility in general. This encapsulation is of current interest for an implantable blood glucose measuring system based on the piezoresistive pressure sensor chip containing a glucose-sensitive hydrogel in its cavity. © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license © 2016 The Authors. Published by Elsevier Ltd. (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-reviewunder underresponsibility responsibility organizing committee of Biosensors Peer-review of of thethe organizing committee of Biosensors 20162016. Keywords: biocompatible encapsulation, parylene C, amphiphilic block copolymers
1. Main text The treatment of metabolic diseases, such as diabetes mellitus, needs especially a simultaneous and continuous monitoring of the different metabolism-related parameters (blood glucose level, pH value and carbon dioxide partial pressure). In this regard, new and mainly rewarding sensor arrays based on a hydrogel swelling attract the main
* Corresponding author. Tel.: +49 351 463 43798; fax: +49 351 463 32320. E-mail address: [email protected]
2212-0173 © 2017 The Authors. 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 Biosensors 2016 doi:10.1016/j.protcy.2017.04.020
C. Jorsch et al. / Procedia Technology 27 (2017) 42 – 43
interest for the on-line applications in the medical diagnostics. Therefore, the efforts in this work were made to improve a miniaturized implantable sensor array microsystem consisting of several hydrogel-based sensors. The working principle of the sensors as well as the type of the stimuli-responsive hydrogel depends on the applications, such as temperature sensor, pH sensor, glucose sensor and more. [1, 2] Each of them has an integrated piezoresistive Wheatstone bridge at the surface of the flexure plate which acts as mechano-electrical transducer for the transformation of the plate deflection into an electrical output voltage Vout. [3] The stimuli-responsive hydrogel swells and deflects the bending plate. The whole sensor system is featured with a biocompatible encapsulation needed for the device implantation into the human body. A multi-layer sensor encapsulation consisting of parylene C and amphiphilic block-copolymers (Fig. 1b) was proposed for subcutaneous implants and characterized using contact angle measurements (Fig. 1a), atomic force microscopy and X-ray photoelectron spectroscopy. The coupling of these polymers to mostly inert parylene C was successfully performed by means of the developed coating procedure. With the coupling of different polymers, the change of surface characteristics was observed. Biocompatibility studies with human fibroblast cells were performed to indicate cell-based reactions referable to the future implant material. Figure 1c shows for block-copolymer samples just 20 % less cell viability, while the decrease on parylene C surface is around 40%. In order to understand the behaviour of implants at physiological conditions, the interaction of the implant surface with biological objects like proteins, serum and blood plasma is discussed taking into account a possible protein adsorption on the implant surface due to the tissue inflammation around the implant, which should be minimized.
Fig. 1. (a) Contact angle measurements with water on parylene C, θ = 90.0 ° (left) and on parylene C/amphiphilic block copolymer, θ = 44.3 ° (right); (b) Structural formula of the block copolymer PEG114-b-p(L-Glu)40-b-p(L-Leu)10; (c) Fluorescence intensity (Cell Titer Blue Assay) as an indicator for the cell viability after the direct incubation on the coated biomaterials (n=6).
The biocompatibility of implant-material plays a major role in design and development of implantable devices. Biocompatibility studies performed in this work showed that the proposed surface modification is useful for all types of implants. Acknowledgements The authors thank the Deutsche Forschungsgemeinschaft (DFG) fort the financial support (RTG 1865 “Hydrogel based microsystems”). References [1] Gerlach, G. and Arndt, K.-F. (Hg.): Hydrogel Sensors and Actuators. Engineering and Technology. Berlin, Heidelberg: Springer-Verlag, 2009 [2] Lin, G.; Chang, S.; Hao, H.; Tathireddy, P.; Orthner, M.; Magda, J.; Solzbacher, F.: Osmotic swelling pressure response of smart hydrogels suitable for chronically implantable glucose sensors. Sensors and Actuators B: Chemical 144 (1), 332–336, 2010. [3] Guenther M., Wallmersperger T., Gerlach G.: Piezoresistive chemical sensors based on functionalized hydrogels, Chemosensors, 2(2) 145170. 2014.
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