Lab-on-a-Chip Systems

Tuesday, 23 June 2015 22:09

On this page you will find publications dealing with tiny cell or organ system developments on microchips. Aim of these developments is to connect all important human organs on the chip with smallest blood vessels to use them for toxicity testing in the future. Therefore this will be reduce or even terminate animal consumption.

The chip systems can also be used in basic research, for instance to study human diseases with appropriate cell or organ systems expressing the disease phenomenon which are apllied to the chip.

The reader is also referred to our news releases and working groups on this topic.


Johan U. Lind, Travis A. Busbee, Alexander D. Valentine et al. (2016): Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing. Nature Materials.

Frey O., Misun P. M., Fluri D. A., Hengstler J. G. & Hierlemann A. (2014): Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nature Communications 5: 4250. doi: 10.1038/ncomms5250.

K. Schimek, M. Busek, S. Brincker, B. Groth, S. Hoffmann, R. Lauster, G. Lindner, A. Lorenz, U. Menzel, F. Sonntag, H. Walles, U. Marx and R. Horland (2013): Integrating biological vasculature into a multi-organ-chip microsystem; Lab Chip.

E. Materne, A. Tonevitsky and U. Marx (2013): Chip-based liver equivalents for toxicity testing - organotypicalness versus cost-efficient high throughput; Lab Chip.

I. Wagner, E. Materne, S. Brincker, U. Süßbier, C. Frädrich, M. Busek, F. Sonntag, D. Sakharov, E. Trushkin, A. Tonevitsky, R. Lauster, U. Marx (2013): A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture; Lab Chip.

B. Ataҫ, I. Wagner, R. Horland, R. Lauster, U. Marx, A. Tonevitsky, A. Azar, G. Lindner (2013): Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion; Lab Chip.

U. Marx, H. Walles, S. Hoffmann, G. Lindner, R. Horland, F. Sonntag, U. Klotzbach, D. Sakharov, A. Tonevitsky, R. Lauster (2012): 'Human-on-a-chip' developments: a translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substances in laboratory animals and man?; Alternatives to Lab Animals.

K.V. Gernaey, F. Baganz, E. Franco-Lara, F. Kensy, U. Krühne, M. Luebberstedt, U. Marx, E. Palmqvist, A. Schmid, F. Schubert, C.F. Mandenius (2012): Monitoring and control of microbioreactors: an expert opinion on development needs; Biotechnology Journal.

R. Horland, G. Lindner, I. Wagner, B. Atac, S. Hoffmann, M. Gruchow, F. Sonntag, U. Klotzbach, R. Lauster, U. Marx (2011): Human hair follicle equivalents in vitro for transplantation and chip-based substance testing; BMC Proceedings.

M. Pilarek, P. Neubauer, U. Marx (2011): Biological cardio-micro-pumps for micro­bio­reactors and analytical micro-systems; Sensors and Actuators.

F. Sonntag, M. Gruchow, I. Wagner, G. Lindner, U. Marx (2011): Miniaturisierte humane organtypische Zell- und Gewebekulturen; BIOspektrum.

F. Sonntag, N. Schilling, K. Mader, M. Gruchow, U. Klotzbach, G. Lindner, R. Horland, I. Wagner, R. Lauster, S. Howitz, S. Hoffmann, U. Marx (2010): Design and prototyping of a chip-besed multi-micro-organoid culture system for substance testing, predictive to human (substance) exposure; Journal of Biotechnology.

Ground-breaking Technology

Monday, 23 June 2014 22:20

With this page InVitro+Jobs offers information about "future-oriented developments". In this section, we'll focus on developments which have the potential to replace animal use in a particular field in the near future.

Innovative imaging methods could replace animal use (e.g. the use of non-human primates) with human-specific, non-invasive techniques in several fields of cognitive neuroscience.

Here you find literature sources that lead to the abstract.

The imaging techniques, however, require further testing to be accepted as animal replacement methods. Currently there are no studies reported and no evaluations or validations are known.

Photo: Kasuga Huang.

1. Imaging Methods

Bisdas S, Lá Fougere C & Ernemann U (2015): Hybrid MR-PET in Neuroimaging. Clin Neuroradiol. 2015 Oct; 25 Suppl 2:275-81. doi: 10.1007/s00062-015-0427-6. Epub 2015 Jul 31.

Bouchard, M. B., Voleti, V., Mendes, C. S., Lacefield, C., Grueber, W. B., Mann, R. S., Bruno, R. M. & Hillman, E. C. M. (2015): Swept confocally-aligned planar excitation (SCAPE) microscopy for high-speed volumetric imaging of behaving organisms. Nature Photonics, DOI: 10.1038/nphoton.2014.323

Chang BJ, Perez Meza VD, Stelzer EHK (2017): csiLSFM combines light-sheet fluorescence microscopy and coherent structured illumination for a lateral resolution below 100 nm. Proc Natl Acad Sci USA, 114 (19): 4869-4874. (2017 May 9). Epub 2017 Apr 24.

Chhatwal, J. P., Schultz, A. P., Johnson, K., Benzinger, T. L. S., Jack, Jr., C., Ances, B. M., Sullivan, C. A., Salloway, S. P., Ringman, J. M., Koeppe, R. A., Marcus, D. S., Thompson, P., Saykin, A. J., Correia, S., Schofield, P. R., Rowe, C. C., Fox, N. C., Brickman, A. M., Mayeux, R., McDade, E., Bateman, R., Fagan, A. M., Goate, A. M., Xiong, C., Buckles, V. D., Morris, J., C. & Sperling, R. A. (2013): Impaired default network functional connectivity in autosomal dominant Alzheimer disease. Neurology 81. DOI 10.1212/WNL.0b013e3182a1aafe

Choi, Woo June & Wang, Ruikang K. (2015): Swept-source optical coherence tomography powered by a 1.3-μm vertical cavity surface emitting laser enables 2.3-mm-deep brain imaging in mice in vivo. J. Biomed. Opt. 20(10), 106004 (Oct 08, 2015). doi:10.1117/1.JBO.20.10.106004

Chojnacki, J., Staudt, T., Glass, B., Bingen, P., Engelhardt, J., Anders, M., Schneider, J., Müller, B., Hell, S. W. & Kräusslich, H.-G. (2012): Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy. Science 338/6106: 524-528.

Connolly, C. G., Wu, J., Ho, T. C., Hoeft, F., Wolkowitz, O. Eisendrath, S., Frank, G., Hendren, R., Max, J. E., Paulus, M. P., Tapert, S. F. Banerjee, D., Simmons, A. N. & Yang, T. T. (2013): Resting-State Functional Connectivity of Subgenual Anterior Cingulate Cortex in Depressed Adolescents. Biol. Psychiatry.

de Winkel, K.N., Nesti, A., Ayaz, H. & Bülthoff, H. H. (2017): Neural correlates of decision making on whole body yaw rotation: an fNIRS study. Neuroscience Letters, Available online 13 June 2017

Derix, J., Yang, S., Lüsebrink, F., Fiederer, L. D. J., Schulze-Bonhage, A., Aertsen, A., Speck, O. and Ball, T. (2014): Visualization of the amygdalo–hippocampal border and its structural variability by 7T and 3T magnetic resonance imaging. Hum. Brain Mapp. Early View (Online Version of Record published before inclusion in an issue). DOI: 10.1002/hbm.22477

Downing, P., Liu, J., & Kanwisher, N. (2001): Testing cognitive models of visual attention with fMRI and MEG. Neuropsychologia, 39/12: 1329-1342.

Espy, M., Matlachov, A., Volegov, P., Mosher, J.C., & Kraus, R.H., Jr. (2005): SQUID-based simultaneous detection of NMR and biomagnetic signals at ultra-low magnetic fields. IEEE Trans. Appl. Supercond., 15: 635-639.

Haynes, J.D. & Rees, G. (2005): Predicting the orientation of invisible stimuli from activity in human primary visual cortex. Nat.Neurosci., 8/5: 686-691.

Heinz, A., Siessmeier, T., Wrase, J., Hermann, D., Klein, S., Grusser, S. M., Flor, H., Braus, D. F., Buchholz, H. G., Grunder, G., Schreckenberger, M., Smolka, M. N., Rosch, F., Mann, K., & Bartenstein, P. (2004): Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry, 161/10: 1783-1789.

Höfner, N., Albrecht, H. H., Cassara, A. M., Curio, G., Hartwig, S., Haueisen, J., Hilschenz, I., Korber, R., Martens, S., Scheer, H. J., Voigt, J., Trahms, L., & Burghoff, M. (2011): Are brain currents detectable by means of low-field NMR? A phantom study. Magn Reson. Imaging 29/10: 1365-1373.

Kaiplavil, Sreekumar & Mandelis, Andreas (2014): Truncated-correlation photothermal coherence tomography for deep subsurface analysis. Nature Photonics. doi:10.1038/nphoton.2014.111

Kamitani, Y. & Tong, F. (2006): Decoding seen and attended motion directions from activity in the human visual cortex. Curr.Biol, 16/11: 1096-1102.

Klippel, S., Döpfert, J., Jabadurai Jayapaul, J., Kunth, M., Rossella, F., Schnurr, M., Witte, C., Freund, C. & Schröder, L. (2013: Cell tracking with Caged Xenon: Using Cryptophanes as MRI Reporters upon Cellular Internalization.(Epub ahead of print) DOI:10.1002/anie.201307290

König, K & Ostendorf, A (Eds.): Optically Induced Nanostructures. Biomedical and Technical Applications. Verlag DeGruyter (2015).

Kraus, R.H., Jr., Volegov, P., Matlachov, A., & Espy, M. (2008): Toward direct neural current imaging by resonant mechanisms at ultra-low field. Neuroimage., 39/1: 310-317.

Le Bihan, D., Mangin, J.-F., Poupon, C., Clark, C. A., Pappata, S., Molko, N., & Chabriat, H. (2001): Diffusion Tensor Imaging: Concepts and Applications. Journal of Magnetic Resonance Imaging. 13: 534–546.

Lee, M. H., Smyser, C. D. & Shimony, J. S. (2012): Resting-State fMRI: A Review of Methods and Clinical Applications. AJNR Am. J. Neuroradiol. 10.3174/ajnr.A3263

Lee, T, Cai, LX, Lelyveld, VS, Aviad Hai & Alan Jasanoff (2014): Molecular-Level Functional Magnetic Resonance Imaging of Dopaminergic Signaling. Science 344: 533-535.

Liangzhong Xiang, Bo Wang, Lijun Ji & Huabei Jiang (2013): 4-D Photoacoustic Tomography. Scientific Reports 3 : 1113, DOI: 10.1038/srep01113

Loretz, M., Rosskopf, T., Boss, J.M., Pezzagna, S., Meijer, J. & C. L. Degen (2014): Single-proton spin detection by diamond magnetometry. Science Express Reports. doi: 10.1126/science.1259464

Mahamid, J., Pfeffer, S., Schaffer, M., Villa, E., Danev, R., Kuhn-Cuellar, L., Förster, F., Hyman, A. A., Plitzko, J. M., Baumeister, W. (2016): Visualizing the molecular sociology at the HeLa cell nuclear periphery. Science 351 (6276): 969-972. DOI: 10.1126/science.aad8857

Nielles-Vallespin, S., Mekkaoui,C., Gatehouse, P., Reese, T. G., Keegan, J., Ferreira, P. F., Collins, S., Speier, P., Feiweier, T., de Silva, R., Jackowski, M. P., Pennell, D. J., Sosnovik, D. E. & Firmin, D. (2013): In Vivo Diffusion Tensor MRI of the Human Heart: Reproducibility of Breath-Hold and Navigator-Based Approaches. Magnetic Resonance in Medicine. 70:454–465.

Patching, Simon G. (2014): Surface plasmon resonance spectroscopy for characterisation of membrane protein–ligand interactions and its potential for drug discovery. Biochimica et Biophysica Acta 1838: 43–55.

Schindler, A. & Bartels, A. (2013): Parietal Cortex Codes for Egocentric Space beyond the Field of View. Current Biology 23, 1–6.

Schneider, J., Zahn, J., Maglione, M., Sigrist, S. J., Marquard, J., Chojnacki, J.,  Kräusslich, H.-G., Sahl, S. J., Engelhardt, J. & Hell, S. W.
(2015): Ultrafast, temporally stochastic STED nanoscopy of millisecond dynamics. Nature Methods 2015, 10.1038/nmeth.3481

Shibata, M., Uchihashi, T., Ando, T. & Yasuda, R. (2015): Long-tip high-speed atomic force microscopy for nanometer-scale imaging in live cells. SCIENTIFIC REPORTS 5: 8724, DOI: 10.1038/srep08724.

Stirman, JN, Smith, IT, Kudenov, MW & Smith, SL (2016): Wide field-of-view, multi-region, two-photon imaging of neuronal activity in the mammalian brain. Nature Biotechnology, advance online publication, doi:10.1038/nbt.3594.

Stratis Tzoumas, Antonio Nunes, Ivan Olefir, Stefan Stangl, Panagiotis Symvoulidis, Sarah Glasl, Christine Bayer, Gabriele Multhoff & Vasilis Ntziachristos (2016): Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues. Nature Communications 7, Article number: 12121 doi:10.1038/ncomms12121.

-> New: Thunemann M, Schörg BF, Feil S, Lin Y, Voelkl J, Golla M, Vachaviolos A, Kohlhofer U, Quintanilla-Martinez L, Olbrich M, Ehrlichmann W, Reischl G, Griessinger CM, Langer HF, Gawaz M, Lang F, Schäfers M, Kneilling M, Pichler BJ, Feil R. (2017): Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography. Nature Communications. DOI: 10.1038/s41467-017-00482-y.

Tong, F. Harrison S. A., Dewey, J. A., Kamitani, Y (2013): Relationship between BOLD amplitude and pattern classification of orientation-selective activity in the human visual cortex. NeuroImage 63 (2012) 1212–1222.

Wehrl, H. F., Hossain, M., Lankes, K., Liu, C.-C., Bezrukov, I., Martirosian, P., Schick, F., Reischl, G. & Pichler, B. J. (2013): Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales. Nature Medicine.

Weizenecker, J., Gleich, B., Rahmer, J., Dahnke, H. & Borgert, J. (2009): Three-dimensional real-time in vivo magnetic particle imaging. Phys. Med. Biol. 54 (2009) L1–L10.

Photo: Paul Wicks.

2. Non-invasive Brain-Computer Interface

Herff, C, Heger, D, de Pesters, A, Telaar, D, Brunner, P, Schalk, G & Schultz, T. (2015): Brain-to-text: decoding spoken phrases from phone representations in the brain. Front. Neurosci.

Quandt, F., Reichert, C., Hinrichs, H., Heinze, H.J., Knight, R.T., & Rieger, J. W. (2012): Single trial discrimination of individual finger movements on one hand: a combined MEG and EEG study. Neuroimage., 59/4: 3316-3324.

Waldert, S., Preissl, H., Demandt, E., Braun, C., Birbaumer, N., Aertsen, A., & Mehring, C. (2008): Hand movement direction decoded from MEG and EEG. J Neurosci., 28/4: 1000-1008.

3. Non-Invasive Procedures for Brain Stimulation

Tufail, Y., Matyushov, A., Baldwin, N., Tauchmann, M. L., Georges, J., Yoshihiro, A., Tillery, S. I., & Tyler, W. J. (2010): Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron, 66/5: 681-694.

Photo: Sven Hoppe,

4. Human-specific Disease Models (Diseases-in-a-dish)

Callaway, E. (2011): Cells snag top modelling job. Nature 469/7330: 279.

Se Hoon Choi, Young Hye Kim, Matthias Hebisch, Christopher Sliwinski, Seungkyu Lee, Carla D’Avanzo, Hechao Chen, Basavaraj Hooli, Caroline Asselin, Julien Muffat, Justin B. Klee, Can Zhang, Brian J. Wainger, Michael Peitz, Dora M. Kovacs, Clifford J. Woolf, Steven L. Wagner, Rudolph E. Tanzi & Doo Yeon Kim (2014): A three-dimensional human neural cell culture model of Alzheimer’s disease. doi:10.1038/nature13800

-> Neu: Dekkers, JF, Berkers, G, Kruisselbrink, E, et al. (2016): Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Science 8/344.

-> Neu: Graffmann N, Ring S, Kawala MA, Wruck W, Ncube A, Trompeter HI, et al. (2016): Modelling NAFLD with human pluripotent stem cell derived immature hepatocyte like cells reveals activation of PLIN2 and confirms regulatory functions of PPARalpha. Stem cells and development.

D. Huh, D. C. Leslie, B. D. Matthews, J. P. Fraser, S. Jurek, G. A. Hamilton, K. S. Thorneloe, M. A. McAlexander, D. E. Ingber, A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice. Sci. Transl. Med. 4, 159ra147 (2012).

Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., Feldman, O., Gepstein, A., Arbel, G., Hammerman, H., Boulos, M., & Gepstein, L. (2011): Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471/7337: 225-229.

Jerome Mertens, Apuã C.M. Paquola, Manching Ku, Emily Hatch, Lena Böhnke, Shauheen Ladjevardi, Sean McGrath, Benjamin Campbell, Hyungjun Lee, Joseph R. Herdy, J. Tiago Goncalves, Tomohisa Toda, Yongsung Kim, Jürgen Winkler, Jun Yao, Martin Hetzer, and Fred H. Gage (2015): Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects. Cell Stem Cell DOI:

Moretti, A., Bellin, M., Welling, A., Jung, C.B., Lam, J.T., Bott-Flugel, L., Dorn, T., Goedel, A., Hohnke, C., Hofmann, F., Seyfarth, M., Sinnecker, D., Schomig, A., & Laugwitz, K.L. (2010): Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl. J Med 363/15: 1397-1409.

Nguyen, D.-H. T., Stapleton, S. C., Yang, M. T., Cha, S. S., Choi, C. K., Galie, P. A. & Chen, C. S. (2013): Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. PNAS 110/17: 6712-6717.

Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007): Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131/5: 861-872.

Wang, G., McCain, M., et. al. (2014): Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-a-chip technologies. Nature Medicine.


5. Microfluidic systems

Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y., & Ingber, D. E. (2010): Reconstituting organ-level lung functions on a chip. Science, 328/5986: 1662-1668.

Huh, D., Hamilton, G. A., & Ingber, D. E. (2011): From 3D cell culture to organs-on-chips. Trends Cell Biol, 21/12: 745-754.

Neuzil, P. et al. (2012): Revisiting lab-on-a-chip technology for drug discovery. Nat Rev Drug Discov. 11: 620 - 32.

-> Neu: Friedrich Schuler, Frank Schwemmer, Martin Trotter, Simon Wadle, Roland Zengerle, Felix von Stetten und Nils Paust (2015): Centrifugal step emulsification applied for absolute quantification of nucleic acids by digital droplet RPA. Lab Chip, 2015,15, 2759-2766. DOI: 10.1039/C5LC00291E

Tsai, M., Kita, A., Leach, J., Rounsevell, R., Huang, J. N., Moake, J., Ware, R. E., Fletcher, D. A., & Lam, W. A. (2012): In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. J Clin Invest, 122/1: 408-418.