Sunday, March 24, 2013

Towards a Human Body on a Chip - Part III

Creating a human body on a chip is the dream of some researchers. In the first part of this series, I talked about the lung on a chip device and how we can improve the current drug development model by building those organ on a chip devices. Combining the chips to create an ultimate human body on a chip platform will speed up the drug development progress, end drug testing on animals and make drug testing more reliable. The second part described some of the ongoing problems with these device and how they can be solved. In the last part of this series, I will focus on the current status of this research. What has been done so far? How far are we into commercializing these products? What's left to do?

Which organ on a chip devices are out there?

The most-advanced organ on a chip device is currently the lung, developed by scientists at the Wyss Institute. Another device created by the same scientists is the gut on a chip (shown below). This chip is made of PDMS (a flexible polymer commonly used in microfluidics) and features microfluidic channels. In the image below you see two different colored fluids running inside the channel and exiting on the bottom. The structure of this chip is very similar to the lung on a chip developed by the same group. It has two channels (red and blue), one is running on top of the other one. In between there is a horizontally aligned porous membrane lined with real human intestinal epithelial cells. On the side of the colored channels are two chambers which can be pressurized in a cyclical motion to mimic the digestion happening in our body. These two are the most advanced organ on a chip devices out there. Scientists are also working on creating artificial muscles to mimic the movement in the heart, as well as on organs like the kidney, liver and bones.

Gut on a chip device
Image courtesy: Wyss Institute
Who is investing in the human on a chip?

In July 2013, DARPA (Defense Advanced Research Projects Agency, USA) announced a $37 million grant for the Wyss Institute at Harward for the development of an array of organ on a chip devices. The Wyss Institute has already developed a lung, as well as the gut on a chip device above. Further projects will include the heart, liver and kidney. Furthermore, they are developing chips that will mimic the human skin and muscles. The NIH (National Institute of Health, USA) also funded several researchers all over the country to develop organ on a chip devices. Their total funding amount was $13 million. The European Union is also funding a Switzerland based company, called InSphero AG with €1.4million for 3 years (starting June 2012). InSphero is focusing to solve the 3D structure implementation of the cell cultures, one of the main problems of current devices (see part II).

What is left to do?

To create a human body on a chip, several organs have to be fabricated, including the lung, heart, bones, kidney, liver, gut (see below). Other devices of interest are the skin, arteries and muscles. Ultimately, all of these single device will be connected via tubes to each other to form the human body on a chip. 

Concept for the human body on a chip.
Image from: D.E.Ingber, Trends in Cell Biology (2011) 21, 12, p. 745-754
Challenging and complex organs like the heart have not been fabricated in full detail yet. It will still take some years to form a complete human body on a chip, but more and more parts are ready to be commercially available and already help transforming the drug testing method. It will be incredible and exciting to follow this development.  

Tuesday, March 19, 2013

Towards a Human Body on a chip - Part II

Is the revolution among us?

This is part II of the series about how we can accelerate the current drug development strategy by building a human body on a chip. The current drug development model is mainly based on animal testing and intensive clinical studies afterwards. Testing new drugs on animals is not only an ethical issue, but also faces crucial problems, as animals are similar to humans but do not react quite the same on new drugs than we do. Therefore, many scientists focus on designing a human body on a chip which can simulate parts of the body without the need of animal testing. By combining microfluidic chips (see my intro to microfluidics) that features the function for parts of our body, like the lung, the gastrointestinal tract or the heart, new drugs can be tested on human like models. In my last entry, the lung on a chip was described, check out the post

How far along are we with organ on a chip device?

Some of you might think that it is still a long way to go until these chips are being used for real applications. You're wrong! This revolution is already among us. In January, researchers from the Institute of Bioengineering and Nanotechnology (IBN) in Singapore have announced that they are partnering with Johnson and Hoffman La-Roche, two big pharmaceutical companies to produce and test the first commercially available liver on a chip. The liver is an important organ for the dug development, as this is the stage where all drugs are being detoxified. Harmfull substances will be reduced, however if a drug is toxic to the body and can't be detoxified by the liver, the human is in danger. Therefore, it is crucial to test new drugs on the liver to see the effect of it's toxicity.

What are the main problems?

One of the main problem in designing organ on a chip devices, is to replicate the important functions of the organ in very great detail. Especially the cells are of importance, as these interact with the drug and determine if the drug is good or bad for your body. The problem with cell cultures in a lab is that they are usually grown in a petri dish, this is a round plastic dish with a gel (called agra) which includes all the nutrients necessary for the cells to survice and grow happily. However, these cells are grown on a flat substrate, that means they can not grow as a cell network (3D) in all directions possible and therefore might not behave like they would in an organ. The researchers from IBN solve this issue by using a foam like structure, called hydroxylpropyl cellulose, which is a FDA approved materials and the building block of cotton and paper. Liver cells can naturally grow within the 3D structure of the material and therefore act more like they would in a real liver.

Sony invests in organ on a chip development

One more thing on the side note to convince you further that these organ on a chip are a promising tool for future drug testing. Yesterday, Sony announced that they are partnering with the Wyss Institute at Harvard University to develop new organ on a chips. The lung on a chip, described in my last post, was developed by researchers from the Wyss Institute. 18 months ago, Sony started to invest in life-science companies, especially those working in microfluidics and life-science technology, e.g. Micronics. The development towards the human body on a chip is definitely a very fascinating and exciting route to follow. 

Sunday, February 17, 2013

Towards a Human Body on a Chip - Part I

How can we accelerate the current drug development model?

Before a pharmaceutical company will test a new drug on humans, it is most commonly tested on small animals. However, these animals may not react on the drug the same way as humans do. It would be much more reliable to test theses drugs directly on humans, but this would be too dangerous as the not yet approved drug might harm the person.

To overcome these issues, researchers are developing human-like systems to mimik parts of our body, like the lung, human intestine or a kidney. These device are called body on a chip or organ on a chip. The major technique behind these chip is microfluidics (check out my post on microfluidics to get a nice intro). One can see these chips as building blocks for something bigger. The aim of this research area is to connect the devices together to create a human on a chip, a human-like working system which is able to mimik parts of our body for drug testing purposes. This way we might even eliminate the use of animals for drug testing to avoid ethical issues. In my next few posts, I will introduce body-on-a-chip platforms which have been developed already and will explain how they work. I would like to start with a very important organ, our lung.

How can you mimik a human lung?

The lung is the crucial respiratory organ in our body. It's main function is to bring fresh oxygen from the air you breath in to the blood and get rid of carbon dioxide or other waster gases that your body does not need when you breath out. In June 2010, researchers from the Wyss Institute at Harvard have developed the very first lung on a chip. The microfluidic device is made using a flexible see-through polymer. The device features one main channel in the center which is divided by a thin membrane into two parts (see picture below). The membrane has small holes inside to let oxygen and other particles flow between the two compartments. On the top side of the membrane, lung cells are attached to the membrane whereas on the bottom side, human capillary cells are attached. Air flows through the top part and human blood through the bottom part. The two channels labeled "vacuum" on the sides are pressurized periodically and will deform the center channel to mimik breathing. 

Principle of the lung on a chip device.
Image courtesy of the Wyss Institute. 
What can you test with a lung on a chip?

The testing spectrum of the lung on a chip device is wide. For instance, one can analyze the influence of environmental pollutions on the lung. One can also model diseases which occur in the lung to see how a drug is affecting the lung cells and how it is healing the system. One major advantage is the transparency of the device, as you can see in the image below. The lung function can be directly monitored under a microscope in real-time. Traditionally, a biopsy is needed in order to see the direct effect of a drug on the body.  

Actual microfluidic lung on a chip device.
Image courtesy of the Wyss Institute. 
With this lung on a chip, pharmaceutical companies can directly test their drugs on a human like lung without the need of testing it on animals. The current drug development model is in a crisis, as it costs millions of dollar and takes many years to pass a drug from the animal testing phase to the human trial phase. The animal model is poor and most of the drugs fail the human test. The lung on a chip device could prevent animal testing and would allow the pharmaceutical companies to directly test on a human model which would be less time-consuming, much cheaper and eliminate the use of animals for testing.