KEYWORDS: Microfluidics, Sensors, Oxygen, Magnetic sensors, Chemical elements, Drug development, 3D acquisition, Lab on a chip, Microscopy, Luminescence
Cell-based assays and organ-like substrates gather increasing attention due to their potentials in diagnostic and drug development. The use of these cell-based systems will allow to better understand in-vivo processes and to test for the direct influence of different substances on cell viability or metabolic activity e.g. in drug development and in addition to identify the influence of generated metabolites or different cell types. In this paper we present a respective technical platform, which enables the use of such cell-based assays. The platform is based on a microfluidic cell-assay toolbox, designed in a fashion allowing to minimize manual steps for cell culture on chip. Elements being essential for this work include membrane elements integrated into a microfluidic device for the separation of liquid stream together with a targeted supply of reagents and a three dimensional feeding of embedded cells. The influence of the metabolism from one cell type on the other can be evaluated due to the arrangement of cell compartments as interacting networks. A respective Lab-on-a-chip handling platform allows for the direct manipulation on a microscope stage and an incubator-free cell culture. Furthermore, luminescent sensors represent promising tools to be embedded into the microfluidic system to monitor the on-chip conditions or to provide information on cell viability and metabolic activity. Finally, examples for implemented assays on chip will be presented, ranging from cell culture showing the cell behavior in respect to surface functionalization and different growth conditions to finally embedding organ-on-chip structures of cultured cell lines.
Torsten Mayr, Tobias Abel, Birgit Ungerböck, Martin Sagmeister, Verena Charwat, Peter Ertl, Elke Kraker, Stefan Köstler, Andreas Tschepp, Bernhard Lamprecht
The recent advances on a monolithically integrated sensor platform based on ring-shaped organic photo detectors are
presented. Various sensing chemistries based on luminescence for the detection of a number of parameters such as
oxygen, carbon dioxide, humidity and pH in gaseous and/or liquid phase were investigated and optimized to the
requirements of the sensor platform. Aiming on practical application, the need and methods to reference luminescence signals are evaluated including two wavelength rationing and lifetime measurements. Finally, we will discuss potential applications of the platform and present a micro-fluidic chip containing an array of integrated sensor spots and organic photodiodes.
Bernhard Lamprecht, Martin Sagmeister, Elke Kraker, Paul Hartmann, Georg Jakopic, Stefan Köstler, Harald Ditlbacher, Nicole Galler, Joachim Krenn, Birgit Ungerböck, Tobias Abel, Torsten Mayr
We present a novel waveguide sensor platform, combining monolithically integrated sensor waveguides with thin-film
organic photodiodes on a single substrate. Aiming at the parallel detection of multiple parameters in a single sensor chip
different sensing principles can be applied on the same basic sensor platform. Utilizing absorbance as sensing principle is
demonstrated by an integrated carbon dioxide sensor, fluorescence as sensing principle is demonstrated by an integrated
oxygen sensor. The versatility of this integrated waveguide platform is further demonstrated by employing surface
plasmon resonance as sensing principle, enabling real-time and label-free detection of a wide range of analytes.
Martin Sagmeister, Bernhard Lamprecht, Elke Kraker, Anja Haase, Georg Jakopic, Stefan Köstler, Harald Ditlbacher, Nicole Galler, Tobias Abel, Torsten Mayr
We present an integrated optical sensor platform suitable for the parallel detection of multiple parameters in an array
format. This sensor technology combines fluorescent sensor layers with ring-shaped thin-film organic photodiodes
(OPDs), serving as integrated fluorescence detectors. The sensing layers are deposited by screen-printing on the upper
side of a PET substrate, which is exposed to an analyte, whereas the ring-shaped photodiodes are monolithically
integrated, by vapour phase deposition, on the backside of the transparent substrate, in correct alignment to the sensing
layers. The monolithic integration of sensor layers and detectors on one common substrate as well as the special ring
shaped form of the photodiodes guarantees that a maximum of the fluorescent light emitted from the sensor layers is
collected. A key advantage of the above described sensor geometry is the straightforward potential to realise sensor
arrays for the parallel detection of multiple parameters: different sensor spots are illuminated by commercial LEDs or
alternatively with one large area OLED, and are read-out by individual integrated organic photodiodes, surrounding the
respective sensor layers. Three different sensing principles including absorption, fluorescence and surface plasmon
resonance can be applied in the same basic sensor platform. The functionality of the concept is demonstrated by an
integrated oxygen sensor. Sensor schemes for the analytical parameters carbon dioxide, temperature and ammonia, are
proposed. Efficient front end electronics enabling intensity and time domain detection of sensor signals for the testing
and characterisation of the integrated sensor devices have been developed.
Optoelectronical components and devices based on organic materials offer a wealth of possibilities in terms of
integration, miniaturization and potentially low-cost fabrication for relevant applications, notwithstanding a performance
that may fall short of conventional state-of-the-art systems. In this context we report on progress towards the
combination of surface plasmon resonance (SPR) sensing with a monolithically integrated optical sensor platform based
on organic materials, including an organic light emitting diode, an optical polymer waveguide and an organic photo
diode. Several according components have been developed and demonstrated recently and were exemplarily applied to
fluorescence lifetime detection. Aiming at multianalyte performance we add SPR to this platform, which enables the
sensitive, real-time and label-free detection of a wide range of analytes. The SPR detection scheme is based on a gold
surface sustaining a surface plasmon mode which reacts sensitively to analyte-induced refractive index changes. Here,
we report on the investigation of the sensor response of a 50 nm thick gold film on an 11 μm thick multimode polymer
waveguide. The feasibility of this sensor concept is shown and its sensitivity is estimated from measuring the intensity
transmitted trough the waveguide at a single wavelength. In addition, some further steps towards full integration are
discussed.
A compact, integrated photoluminescence based oxygen sensor, utilizing an organic light emitting device
(OLED) as the light source and an organic photodiode (OPD) as the detection unit, is described. The detection
system of the sensor array consists of an array of circular
screen-printed fluorescent sensor spots surrounded by
organic photodiodes as integrated fluorescence detectors. The OPD originates from the well-known Tang
photodiode, consisting of a stacked layer of copper phthalocyanine (CuPc, p-type material) and perylene
tetracarboxylic bisbenzimidazole (PTCBi, n-type material). An additional layer of tris-8-hydroxyquinolinatoaluminium
(Alq3, n-type material) was inserted between the PTCBi layer and cathode. An ORMOCERR layer
was used as encapsulation layer. For excitation an organic light emitting diode is used. The sensor spot and the
detector are processed on the same flexible substrate. This approach not only simplifies the detection system by
minimizing the numbers of required optical components - no optical filters have to be used for separating the
excitation light and the luminescent emission-, but also has a large potential for low-cost sensor applications.
The feasibility of the concept is demonstrated by an integrated oxygen sensor, indicating good performance.
Sensor schemes for other chemical parameters are proposed.
The performance of an optical sensor device working on the basis of integrated waveguides relies on the efficient
coupling of light into and out of the waveguide. Conventional coupling methods are based on the usage of
optical components such as prisms or gratings. An alternative approach utilizes fluorescent molecules inside
the core material of the waveguide, and thereby avoids complex and time consuming alignment procedures. In
that context the application of fluorescence resonance energy transfer (FRET) enables the effective separation
of excitation and emission light due to a large effective Stokes shift and accordingly small re-absorption of the
dye molecules. Within the framework of the presented work, fluorescent molecules are used to couple light into
a PDMS/polystyrene waveguide system. The dye molecules are optically characterized and embedded into the
waveguide system. It is demonstrated that the position of the molecules relative to the waveguide influences the
amount of light coupled into the system. The efficient coupling of light out of the waveguide is important to guide
the light to a detecting device for directly measuring the optical throughput through the system. Two basic out
coupling principles have been applied, end-face coupling and out coupling at scattering layers. The system has
also been examined by means of ray tracing simulations, which reveal the influence of various system parameters
such as the position of the dye molecules in the waveguide core and optical properties of the materials.
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