Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip.

A complementary cell analysis method has been developed to assess the dynamic interactions of tumor cells with resident tissue and immune cells using optical light scattering and impedance sensing to shed light on tumor cell behavior. The combination of electroanalytical and optical biosensing technologies integrated in a lab-on-a-chip allows for continuous, label-free, and noninvasive probing of dynamic cell-to-cell interactions between adherent and nonadherent cocultures, thus providing real-time insights into tumor cell responses under physiologically relevant conditions. While the study of adherent cocultures is important for the understanding and suppression of metastatic invasion, the analysis of tumor cell interactions with nonadherent immune cells plays a vital role in cancer immunotherapy research. For the first time, the direct cell-to-cell interactions of tumor cells with bead-activated primary T cells were continuously assessed using an effector cell to target a cell ratio of 10:1.

Mobile Ion-Driven Modulation of Electronic Conductivity Explains Long-Timescale Electrical Response in Lead Iodide Perovskite Thick Pellets.

The favorable optoelectronic properties of metal halide perovskites have been used for X- and γ-ray detection, solar energy, and optoelectronics. Large electronic mobility, reduced recombination losses of the electron-hole pairs, and high sensitivity upon ionizing irradiation have fostered great attention on technological realizations. Nevertheless, the recognized mixed ionic-electronic transport properties of hybrid perovskites possess severe limitations as far as long-timescale instabilities and degradation issues are faced. Several effects are attributed to the presence of mobile ions such as shielding of the internal electrical field upon biasing and chemical interaction between intrinsic moving defects and electrode materials. Ion-originated modulations of electronic properties constitute an essential peace of knowledge to further progress into the halide perovskite device physics and operating modes. Here, ionic current and electronic impedance of lead methylammonium iodide perovskite thick pellets are independently monitored, showing self-consistent patterns. Our findings point to a coupling of ionic and electronic properties as a dynamic doping effect caused by moving ions that act as mobile dopants. The electronic doping profile changes within the bulk as a function of the actual ion inner distribution, then producing a specific time dependence in the electronic conductivity that reproduces time patterns of the type ∝t, a clear fingerprint of diffusive transport. Values for the iodine-related defect diffusivity in the range of Dion ∼ 10-8 cm2 s-1, which corresponds to ionic mobilities of about µion ∼ 10-6 cm2 V-1 s-1, are encountered. Technological realizations based on thick perovskite layers would benefit from this fundamental information, as far as long-timescale current stabilization is concerned.

Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing.

Rheumatoid arthritis is a chronic, systemic joint disease in which an autoimmune response translates into an inflammatory attack resulting in joint damage, disability and decreased quality of life. Despite recent introduction of therapeutic agents such as anti-TNFα, even the best current therapies fail to achieve disease remission in most arthritis patients. Therefore, research into the mechanisms governing the destructive inflammatory process in rheumatoid arthritis is of great importance and may reveal novel strategies for the therapeutic interventions. To gain deeper insight into its pathogensis, we have developed for the first time a three-dimensional synovium-on-a-chip system in order to monitor the onset and progression of inflammatory synovial tissue responses. In our study, patient-derived primary synovial organoids are cultivated on a single chip platform containing embedded organic-photodetector arrays for over a week in the absence and presence of tumor-necrosis-factor. Using a label-free and non-invasive optical light-scatter biosensing strategy inflammation-induced 3D tissue-level architectural changes were already detected after two days. We demonstrate that the integration of complex human synovial organ cultures in a lab-on-a-chip provides reproducible and reliable information on how systemic stress factors affect synovial tissue architectures.

High Performance All-Polymer Photodetector Comprising a Donor-Acceptor-Acceptor Structured Indacenodithiophene-Bithieno[3,4-c]Pyrroletetrone Copolymer.

The synthesis of an acceptor polymer PIDT-2TPD, comprising indacenodithiophene (IDT) as the electron-rich unit and an interconnected bithieno[3,4-c]pyrrole-4,4',6,6'-tetrone (2TPD) as the electron-deficient unit, and its application for all-polymer photodetectors is reported. The optical, electrochemical, charge transport, and device properties of a blend of poly(3-hexylthiophene) and PIDT-2TPD are studied. The blend shows strong complementary absorption and balanced electron and hole mobility, which are desired properties for a photoactive layer. The device exhibits dark current density in the order of 10-5 mA/cm2, external quantum efficiency broadly above 30%, and nearly planar detectivity over the entire visible spectral range (maximum of 1.1 × 1012 Jones at 610 nm) under -5 V bias. These results indicate that PIDT-2TPD is a highly functional new type of acceptor and further motivate the use of 2TPD as a building block for other n-type materials.

High-Performance Organic Photodetectors from a High-Bandgap Indacenodithiophene-Based π-Conjugated Donor-Acceptor Polymer.

A conjugated donor-acceptor polymer, poly[4,4,9,9-tetrakis(4-hexylphenyl)-4,9-dihydro- s-indaceno[1,2- b:5,6- b']dithiophene-2,7-diyl- alt-5-(2-ethylhexyl)-4 H-thieno[3,4- c]pyrrole-4,6(5 H)-dione-1,3-diyl] (PIDT-TPD), is blended with the fullerene derivative [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) for the fabrication of thin and solution-processed organic photodetectors (OPDs). Systematic screening of the concentration ratio of the blend and the molecular weight of the polymer is performed to optimize the active layer morphology and the OPD performance. The device comprising a medium molecular weight polymer (27.0 kg/mol) in a PIDT-TPD:PC61BM 1:1 ratio exhibits an external quantum efficiency of 52% at 610 nm, a dark current density of 1 nA/cm2, a detectivity of 1.44 × 1013 Jones, and a maximum 3 dB cutoff frequency of 100 kHz at -5 V bias. These results are remarkable among the state-of-the-art red photodetectors based on conjugated polymers. As such, this work presents a functional organic active material for high-speed OPDs with a linear photoresponse at different light intensities.

Standardization of microfluidic cell cultures using integrated organic photodiodes and electrode arrays.

Nanotechnology provides the tools to develop novel biosensors with improved performance, including sensitivity and response time that can be readily integrated into diagnostic devices. We have developed a miniaturized cell analysis platform to advance microfluidic cell cultures by combining two complementary, label-free and non-invasive cell analysis methods for the long-term monitoring of dynamic cell behavior. The novel dual-parameter cell-on-a-chip detects light scattering from adherent cells to provide information on cell numbers and intracellular granularity, while simultaneously performing impedance spectroscopy to monitor cell adhesion and cell-cell interaction. In the present work we have integrated spray-coated organic photodiode arrays with a lab-on-a-chip containing embedded interdigitated electrode structures to improve assay reproducibility, reliability and accuracy. We successfully demonstrate that the complementary cell chip technology can accurately detect cell numbers, clarify misleading results during cell-substance interaction assays, as well as the cytotoxicity screening of drug substances. The ability to precisely determine cell numbers within minutes constitutes a major step towards standardization.

Interface trap states in organic photodiodes.

Organic semiconductors are attractive for optical sensing applications due to the effortless processing on large active area of several cm(2), which is difficult to achieve with solid-state devices. However, compared to silicon photodiodes, sensitivity and dynamic behavior remain a major challenge with organic sensors. Here, we show that charge trapping phenomena deteriorate the bandwidth of organic photodiodes (OPDs) to a few Hz at low-light levels. We demonstrate that, despite the large OPD capacitances of ~10 nF cm(-2), a frequency response in the kHz regime can be achieved at light levels as low as 20 nW cm(-2) by appropriate interface engineering, which corresponds to a 1000-fold increase compared to state-of-the-art OPDs. Such device characteristics indicate that large active area OPDs are suitable for industrial sensing and even match medical requirements for single X-ray pulse detection in the millisecond range.

Time-of-flight magnetic flow cytometry in whole blood with integrated sample preparation.

Rapid and specific rare cell detection for point-of-care testing requires an integration of the sample preparation for flow cytometry. To achieve such a challenging goal we have developed a magnetic flow cytometry technique which applies magnetophoresis to perform cell enrichment, focusing, and background elimination in a single step. Time-of-flight measurements are performed with integrated magnetic sensors to detect specifically cancer cells and cell diameters in whole blood.

Fully spray coated organic photodiodes.

Solution-processed organic diodes based on bulk heterojunctions are attractive for large area photodetection. We report a general approach for fully spray-coated organic photodiodes with outstanding characteristics in comparison to bladed or spin-coated devices. Despite the high surface roughness and the less defined morphology of the spray-deposited organic layers, we observe organic photodetectors with responsivities of 0.36 A/W and noise equivalent powers of 0.2 pW/H(1/2) in the visible spectrum at high reverse biases of -5 V. Furthermore, we demonstrate device lifetimes beyond 1 year as well as superior yield and reproducibilties for the dark current and photocurrent densities.