Lab on a Chip Blog

The study of brain development and degeneration is hindered by a lack of physiologically realistic models. French scientists have now developed a way to reconstruct neuronal networks in a microfluidic system to more closely mimic the directional neuronal pathways found in the brain.

Current experimental brain models include neuronal cell cultures and whole animal models; however, the former lack the complex architecture found in vivo, and the latter restrict studies at the cellular level. Aiming to bridge the gap between these models, Jean-Louis Viovy of the Curie Institute, Paris, and coworkers have developed a microfluidic device that allows for the growth of oriented and functional synaptic connections in vitro.

The device consists of two cell culture chambers connected by microchannels, through which axons – nerve fibres that conduct impulses away from the body of the nerve cell – can penetrate to form neuronal networks. In previous setups, replication of the unidirectional networks found in vivo could not be achieved since axons were sent from each chamber to the one opposite, travelling in both directions across the microchannel.

Inspired by the observation that axons can be mechanically constrained, the team modified the device to include asymmetric, funnel-shaped microchannels, termed ‘axon diodes’, to allow axons to grow from only one chamber to the other and not the opposite way. The concept was verified by experiments with mouse cortical neurons, in which the axon projection was 97 per cent selective for the ‘correct’ direction.

Next, by seeding cortical neurons (from the outer part of the brain) on the emitting side of the device and striatal neurons (from the inner part of the brain) on the receiving side, the team demonstrated the reconstruction of an active neuronal pathway involving two different neuronal subtypes. Furthermore, these networks were routinely maintained for three weeks in vitro, which would allow for both short and long-term experimentation.

‘I was struck by the simplicity of the system, it is beautiful,’ remarks Bonnie Firestein, an expert in cellular neurobiology from Rutgers University, New Jersey, US. ‘It is very easy to make and to use, and allows the recreation of what happens in vivo in an in vitro system.’

Such a device has many potential applications in neurobiological research. An initial motivation for this work was the requirement of a model to study the progression of neuronal damage in degenerative diseases such as Alzheimer’s. Additionally, Viovy believes the system is also an important platform for research into brain development and cognitive science. ‘How neurons communicate regarding information transmission is also an area in which we currently lack a model of the kind we have proposed here,’ he says. The team are currently working on further increasing the complexity of the networks, to more accurately model the neuronal organisation of the brain.

Interested? Read Sarah Farley’s full Chemistry World article here or download the Lab on a Chip paper:

Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers
Jean-Michel Peyrin, Bérangère Deleglise, Laure Saias, Maéva Vignes, Paul Gougis, Sebastien Magnifico, Sandrine Betuing, Mathéa Pietri, Jocelyne Caboche, Peter Vanhoutte, Jean-Louis Viovy and Bernard Brugg
Lab Chip, 2011, Advance Article
DOI: 10.1039/c1lc20014c

Another LOC article has been highlighted in Chemistry World!  This article from Mu Chiao and colleagues describes the fabrication of a device that could be implanted behind the eye to release drugs on demand to treat retinal damage caused by diabetes.

Diabetic retinopathy can lead to blindness. A current treatment is laser therapy, which is destructive and results in side effects, such as diminished side and night vision, and unwanted laser burns. Another therapy is to administer antiproliferative drugs, such as docetaxel (normally a cancer drug), but the compounds clear from the blood quickly, so high doses are needed to produce the desired effect, which increases toxicity to other tissues.

Mu Chiao and colleagues from the University of British Columbia in Vancouver have made a device to be implanted behind the eye that releases drugs when triggered by an external magnet. This means that the device doesn’t need a battery and lower doses can be used. Implantable devices have been made before but drug release is done by diffusion and the release rates can’t be controlled, which is a problem if the dosage rate needs to be adjusted when a patient’s condition changes.

To find out more read Elinor Richard’s Chemistry World article or download the article itself here:

On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device
Fatemeh Nazly Pirmoradi, John K. Jackson, Helen M. Burt and Mu Chiao
Lab Chip, 2011, Advance Article
DOI: 10.1039/C1LC20134D

This paper featured in Chemistry World describes a device developed by scientists in China that can control the production of multiple emulsion systems. The system could be used to encapsulate incompatible drug ingredients and to design multi-compartment materials, they say.

Multiple emulsions are liquid systems in which emulsion droplets are placed inside each other, each droplet smaller than the last, creating ‘levels’. Microfluidic devices have been designed to produce such systems, but controlling the number, size and ratio of droplets at each level is difficult, especially when developing a system that has different types of emulsion droplets at the same level. Control over such multi-compartment levels would allow more precise encapsulation and the development of more advanced materials.

Liang-Yin Chu at Sichuan University and colleagues have designed a microfluidic device capable of producing multi-compartment multiple emulsions. Chu says: ‘We hope the novel type of emulsions in our work will open a new gate for the applications of emulsions in the fields of template synthesis, synergistic delivery, micro reactions, bioassay and so on.’

For the full story read Harriet Brewerton’s Chemistry World article or download the paper here:

Controllable microfluidic production of multicomponent multiple emulsions
Wei Wang, Rui Xie, Xiao-Jie Ju, Tao Luo, Li Liu, David A. Weitz and Liang-Yin Chu
Lab Chip, 2011, 11, 1587-1592
DOI: 10.1039/C1LC20065H

The latest LOC article to be highlighted in Chemistry World is Michael Richardson‘s paper showing for the first time that an animal embryo can develop in a microfluidic environment. Their discovery could find application in high-throughput, low-cost assays for drug screening and life sciences research.

Zebrafish embryos are becoming important animal models, bridging the gap between cell culture assays and whole animal testing, and have found use in disease modelling and drug safety prediction assays. These assays are currently performed in microtitre plates and require periodic replacement of the buffer solution, which can cause stress or damage to the embryos. Now, Michael Richardson, from Leiden University, and coworkers have developed a microfluidic lab-on-a-chip device in which the buffer solution can flow continuously through the system, and have successfully raised zebrafish embryos under these conditions.

The team made the device from three layers of borosilicate glass with an array of temperature-controlled wells connected by channels; each well houses a single zebrafish embryo. The growth and development of embryos in the microchip was investigated following a five-day culture. Some minor phenotypic variations, such as reduced body length, were found in the microchip-raised embryos; however, there was no significant increase in other abnormalities compared with control experiments.

To find out more read Sarah Farley’s Chemisty World story here or download the paper:

Zebrafish embryo development in a microfluidic flow-through system
Eric M. Wielhouwer, Shaukat Ali, Abdulrahman Al-Afandi, Marko T. Blom, Marinus B. Olde Riekerink, Christian Poelma, Jerry Westerweel, Johannes Oonk, Elwin X. Vrouwe, Wilfred Buesink, Harald G. J. vanMil, Jonathan Chicken, Ronny van ‘t Oever and Michael K. Richardson
Lab Chip, 2011, Advance Article
DOI: 10.1039/C0LC00443J

Another Lab on a Chip article has been highlighted in Chemistry World!

Human African trypanosomiasis, or sleeping sickness, is caused by parasites in the blood called trypanosomes. The disease is transmitted by tsetse flies and is fatal is left untreated. Standard diagnosis is done by looking for the parasites in blood samples using a microscope. However, the concentration of parasites is often very low, so they need to be separated from the red blood cells before analysis. Many separation methods have been developed, but they are expensive and too complex to use in remote areas where the disease is common.

Jonas Tegenfeldt from the University of Lund, and his colleagues, have developed a microfluidic device that separates the parasites from the blood cells using their shape, because parasites and red blood cells are very difficult to separate by size.

Read Amaya Camara-Campos’ full story online here or go straight to the LOC article:

Separation of parasites from human blood using deterministic lateral displacement
Stefan H. Holm, Jason P. Beech, Michael P. Barrett and Jonas O. Tegenfeldt
Lab Chip, 2011, 11, 1326
DOI: 10.1039/c0lc00560f