Elsevier

Sensors and Actuators B: Chemical

Volume 239, February 2017, Pages 916-922
Sensors and Actuators B: Chemical

Hemocompatibility of EpoCore/EpoClad photoresists on COC substrate for optofluidic integrated Bragg sensors

https://doi.org/10.1016/j.snb.2016.08.113Get rights and content

Highlights

Abstract

We report on the hemocompatibility properties of EpoCore/EpoClad UV-structurable epoxy resins in combination with a TOPAS® cyclic olefin copolymer substrate for potential application as an optofluidic biosensor chip. For comprehensive hemocompatibility tests human blood is directly exposed to layers of the different chip materials up to 3 h. Counts in white blood cells, red blood cells and platelets as well as hemolysis and concentration of thrombin/antithrombin complex (TAT), of complement fragment (C5a) and heparin are determined. Our results attest TOPAS and the epoxy resins high hemocompatibility properties. Subsequently, an optofluidic chip fabrication concept with integrated Bragg grating sensors is suggested. Bragg gratings are directly inscribed into rectangular EpoCore waveguides on TOPAS 6017 substrate by coherent phase mask illumination. UV-structured EpoClad resist serves both as waveguide cladding and microfluidic channel network. In evanescent field refractive index sensing experiments sensitivities up to 76.9 nm/RIU and a maximum refractive index resolution of 1.3·10−5 are achieved by detecting multimode Bragg reflections.

Introduction

Combining microfluidic channels with integrated optical sensor technology in terms of an optical Lab-on-a-chip (LOC) enables high precision optical measurement and monitoring of fluid properties [1], [2]. By exploiting the effect of evanescent field interaction of waveguide modes with the surrounding cladding media, these devices offer an instant detection of changing refractive indices around the waveguide core. In turn, this facilitates sensing applications of fluids as well as adhesion and binding reactions on specific functionalized waveguide surfaces.

Well-defined material choices and robust fabrication processes play crucial roles in creating reliable LOC applications especially when making use of optical refractive index (RI) sensing structures such as, e.g., Bragg gratings [3], Mach-Zehnder interferometers [4] or ring resonators [5]. On the one hand the employed materials have to be chemically stable against the fluids under test, must constitute proper refractive index combinations which allow optical wave guiding and have to be highly transmissive for the optical sensing wavelengths. Moreover, for biosensing purposes the materials must show an adequate biocompatibility. On the other hand it is also necessary that these materials offer an easy microstructure processability at the same time. To fulfill all these strict requirements and thereby keeping the costs low, polymer materials like TOPAS, PMMA, SU8 or PDMS are often employed for LOCs [6], [7], [8].

TOPAS is a cyclic olefin copolymer material which exhibits high chemical resistance and glass transition temperatures up to 170 °C. Due to the very low water absorption (<0.01%) this material suits perfectly for microfluidic applications. Manifold results attest TOPAS an excellent biocompatibility. However, special hemocompatibility data are limited to hemolysis tests only [9].

EpoCore/EpoClad epoxy resins represent an inexpensive UV-patternable negative photoresist combination for optical waveguides featuring low optical losses (∼0.2 dB/cm @ 850 nm), high glass transition temperatures (>180 °C) and an exalted chemical resistance after crosslinking [10]. Fabrication processes of EpoCore waveguides for micro-opto-electro-mechanical systems (MOEMS) [11], spectroscopy applications [12], flexible neural probes [13] and printed circuit boards [14] have been reported so far. However, EpoCore/EpoClad has not been explicitly employed for LOC applications yet. This can be mainly attributed to missing biocompatibility data. Although demanded [13] no biocompatibility tests have been carried out for EpoClad/EpoCore photoresists to the best of the authors' knowledge.

In this work, we therefore comprehensively report on the hemocompatibility properties of TOPAS 6017, EpoCore 10 and EpoClad 10. In addition, a fabrication process for an optofluidic Bragg grating sensor chip comprising these materials is demonstrated. Evanescent field refractive index sensing experiments substantiate the potential of this polymer optical LOC for future biomedical sensing purposes.

Section snippets

Fabrication of optofluidic integrated Bragg sensors

The epoxy photoresists EpoCore 10 and EpoClad 10 are structured photolithographically using an EVG620 mask aligner equipped with an i-line filtered (365 ± 20 nm) mercury vapor lamp. An overview of the single process steps for the fabrication of the optofluidic chip is depicted in Fig. 1. The cyclic olefin copolymer TOPAS 6017 with a thickness of 1 mm is used as substrate material after cleaning in acetone and 2-propanol. EpoCore 10 is spin coated with 10000 rpm for 60 s resulting in a ∼3.0 μm layer

Evanescent refractive index sensing

Fig. 5 comparatively shows the single reflection spectra for the different fluid materials loaded on the EpoCore waveguide integrated Bragg grating area. In air (n  1), three distinct Bragg reflection peaks around 1567.1 nm, 1549.1 nm and 1531.5 nm can be observed which correspond to the fundamental mode and a first and second higher mode with calculated neff of 1.5578, 1.5399 and 1.5224, respectively. While the fundamental mode and first higher mode reflection peaks are very distinct (> 20 dB) the

Conclusion

In this paper, comprehensive hemocompatibility tests for TOPAS 6017, EpoCore 10 and EpoClad 10 are carried out. Taken all results together, the polymers tested alone or in combination can be considered as hemocompatible. Consequently, from the hemocompatibility point of view, biophotonic sensing systems consisting of the polymers tested are highly likely suitable for the projected use with blood specimen. Hence, a combined photolithographic fabrication process for integrated EpoCore Bragg

Acknowledgements

The work at the University of Applied Sciences Aschaffenburg has been supported by the Bayerische Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst KM (grant VIII.2-F116.AS/15/3).

Steffen Hessler received the B.Eng. degree in industrial engineering and M.Eng. degree in electrical engineering from the University of applied sciences Aschaffenburg in 2012 and 2013, respectively. Since 2011 he is a research associate of the local applied laser and photonics group alp. Currently he does his doctor’s degree on polymer optical integrated systems for sensor technology in cooperation with the University of Erlangen-Nuremberg.

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Steffen Hessler received the B.Eng. degree in industrial engineering and M.Eng. degree in electrical engineering from the University of applied sciences Aschaffenburg in 2012 and 2013, respectively. Since 2011 he is a research associate of the local applied laser and photonics group alp. Currently he does his doctor’s degree on polymer optical integrated systems for sensor technology in cooperation with the University of Erlangen-Nuremberg.

Marieke Rüth received a degree in biotechnology (Dipl.-Ing. FH) from the University of Applied Sciences Darmstadt in 2006. In 2008 she joined eXcorLab GmbH (Obernburg, Germany) as laboratory engineer. Since 2013 she is Head of Laboratory at eXcorLab GmbH and received her doctoral degree in cooperation with the Charité − Universitätsmedizin Berlin (Germany) in January 2016.

Christoph Sauvant Dipl. Biol., Ph.D., Physiological Specialist (DPG). In 2006, he made his post-doctoral thesis in the field of renal transport in renal failure at the University of Wuerzburg (Germany). From 2010–2014, he was Head of Experimental Research at the Department of Anaesthesia and Intensive Care at the University Hospital Halle/Saale (Germany). He then joined eXcorLab as Director Research & Development. Since July 2015, he is Managing Director at the eXcorLab GmbH (Obernburg, Germany).

Horst-Dieter Lemke holds a degree in chemistry (Dipl. Chem.) from the University Würzburg from where he also received his doctoral degree in biochemistry in 1981. From 1979–1983 he was working at the Max Planck Institute of Biochemistry (Martinsried, near Munich) followed until 2015 in several positions for Membrana GmbH (Wuppertal), finally as Director Scientific & Clinical Affairs. In 2005 he was cofounder and became Managing Director of eXcorLab GmbH.

Bernhard Schmauss received the Dipl. Ing. and Dr. Ing. degrees in electrical engineering from the University Erlangen-Nuremberg in 1989 and 1995, respectively. Since 2005, he is professor for photonics at the institute of microwaves and photonics of the University Erlangen-Nuremberg. His research interests are fiber lasers, medical application of photonics, optical sensors, few mode fiber propagation and optical transmission systems. He is principal investigator of the “Erlangen Graduate School in Advanced Optical Technologies”.

Ralf Hellmann received the diploma and Dr. degrees in physics from the Philipps University in Marburg in 1992 and 1996. After working for Philips, TDK Electronics and Siemens, he became professor for physics, photonics and laser technology in 2002 at the University of Applied Sciences in Aschaffenburg. His current research interests are photonic technologies, optical sensing and laser material processing. He is head of the Applied Laser and Photonic Group and of the Laser Application Centre and original member of the Fraunhofer Application Centre for Resource Efficiency in Aschaffenburg.

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