Tag Archives: neuronal network

Functional hybrid system that can connect human tissue with electronic devices

I’ve tagged this particular field of interest ‘machine/flesh’ because I find it more descriptive than ‘bio-hybrid system’ which was the term used in a Nov. 15, 2016 news item on phys.org,

One of the biggest challenges in cognitive or rehabilitation neurosciences is the ability to design a functional hybrid system that can connect and exchange information between biological systems, like neurons in the brain, and human-made electronic devices. A large multidisciplinary effort of researchers in Italy brought together physicists, chemists, biochemists, engineers, molecular biologists and physiologists to analyze the biocompatibility of the substrate used to connect these biological and human-made components, and investigate the functionality of the adhering cells, creating a living biohybrid system.

A Nov.15, 2016 American Institute of Physics news release on EurekAlert, which originated the news item, details the investigation,

In an article appearing this week in AIP Advances, from AIP Publishing, the research team used the interaction between light and matter to investigate the material properties at the molecular level using Raman spectroscopy, a technique that, until now, has been principally applied to material science. Thanks to the coupling of the Raman spectrometer with a microscope, spectroscopy becomes a useful tool for investigating micro-objects such as cells and tissues. Raman spectroscopy presents clear advantages for this type of investigation: The molecular composition and the modi?cation of subcellular compartments can be obtained in label-free conditions with non-invasive methods and under physiological conditions, allowing the investigation of a large variety of biological processes both in vitro and in vivo.

Once the biocompatibility of the substrate was analyzed and the functionality of the adhering cells investigated, the next part of this puzzle is connecting with the electronic component. In this case a memristor was used.

“Its name reveals its peculiarity (MEMory ResISTOR), it has a sort of “memory”: depending on the amount of voltage that has been applied to it in the past, it is able to vary its resistance, because of a change of its microscopic physical properties,” said Silvia Caponi, a physicist at the Italian National Research Council in Rome. By combining memristors, it is possible to create pathways within the electrical circuits that work similar to the natural synapses, which develop variable weight in their connections to reproduce the adaptive/learning mechanism. Layers of organic polymers, like polyaniline (PANI) a semiconductor polymer, also have memristive properties, allowing them to work directly with biological materials into a hybrid bio-electronic system.

“We applied the analysis on a hybrid bio-inspired device but in a prospective view, this work provides the proof of concept of an integrated study able to analyse the status of living cells in a large variety of applications that merges nanosciences, neurosciences and bioelectronics,” said Caponi. A natural long-term objective of this work would be interfacing machines and nervous systems as seamlessly as possible.

The multidisciplinary team is ready to build on this proof of principle to realize the potential of memristor networks.

“Once assured the biocompatibility of the materials on which neurons grow,” said Caponi, “we want to define the materials and their functionalization procedures to find the best configuration for the neuron-memristor interface to deliver a full working hybrid bio-memristive system.”

Caption: These are immunofluorescence analysis of SH-SY5Y cells treated for 5 days with 10uM Retinoic Acid and 50ng/ml BDNF for the next 3 days. The DAPI fluorescence stain is blue and Beta-tubulin is green. Credit: Caponi, et al.

Caption: These are immunofluorescence analysis of SH-SY5Y cells treated for 5 days with 10uM Retinoic Acid and 50ng/ml BDNF for the next 3 days. The DAPI fluorescence stain is blue and Beta-tubulin is green. Credit: Caponi, et al.

Here’s a link to and a citation for the paper,

A multidisciplinary approach to study the functional properties of neuron-like cell models constituting a living bio-hybrid system: SH-SY5Y cells adhering to PANI substrate by S. Caponi, S. Mattana, M. Ricci, K. Sagini, L. J. Juarez-Hernandez, A. M. Jimenez-Garduño, N. Cornella, L. Pasquardini, L. Urbanelli, P. Sassi, A. Morresi, C. Emiliani, D. Fioretto, M. Dalla Serra, C. Pederzolli, S. Iannotta, P. Macchi, and C. Musio. AIP Advances 6, 111303 (2016); http://dx.doi.org/10.1063/1.4966587

This paper appears to be open access.

3D brain-on-a-chip from the University of Twente

Dutch researchers have developed a 3D brain-on-a-chip according to a June 23, 2016 news item on Nanowerk,

To study brain cell’s operation and test the effect of medication on individual cells, the conventional Petri dish with flat electrodes is not sufficient. For truly realistic studies, cells have to flourish within three-dimensional surroundings.

Bart Schurink, researcher at University of Twente’s MESA+ Institute for Nanotechnology, has developed a sieve with 900 openings, each of which has the shape of an inverted pyramid. On top of this array of pyramids, a micro-reactor takes care of cell growth. Schurink defends his PhD thesis June 23 [2016].

A June 23, 2016 University of Twente press release, which originated the news item, provides more detail,

A brain-on-a-chip demands more than a series of electrodes in 2D, on which brain cells can be cultured. To mimic the brain in a realistic way, you need facilities for fluid flow, and the cells need some freedom for themselves even when they are kept at predefined spaces. Schurink therefore developed a micro sieve structure with hundreds of openings on a 2 by 2 mm surface. Each of these holes has the shape of  an inverted pyramid. Each pyramid, in turn, is equipped with an electrode, for measuring electrical signals or sending stimuli to the network. At the same time, liquids can flow through tiny holes, needed to capture the cells and for sending nutrients or medication to a single cell.

NEURONAL NETWORK

After neurons have been placed inside all the pyramids, they will start to form a network. This is not just a 2D network between the holes: by placing a micro reactor on top of the sieve, a neuron network can develop in the vertical direction as well. Growth and electrical activity can be monitored subsequently: each individual cell can be identified by the pyramid it is in. Manufacturing this system, demands a lot of both the production facilities at UT’s NanoLab and of creative solutions the designers come up with. For example, finding the proper way of guaranteeing  the same dimensions for every hole, is quite challenging.

Schurink’s new µSEA (micro sieve electrode array) has been tested with living cells, from the brains of laboratory rats. Both the positioning of the cells and neuronal network growth have been tested. The result of this PhD research is a fully new research platform for performing research on the brain, diseases and effects of medication.

Schurink (1982) has conducted his research within the group Meso Scale Chemical Systems, of Prof Han Gardeniers. The group is part of the MESA+ Institute for Nanotechnology of the University of Twente. Schurink’s thesis is titled ‘Microfabrication and microfluidics for 3D brain-on-chip’ …

I have written about one other piece about a ‘3D’ organ-on-a-chip project in China (my Jan. 29, 2016 posting).