Emma Meinke
Human on a Chip Technology Will Revolutionize Drug Testing
Abstract: The “human on a chip” is currently one of the hottest engineering research projects.
It is receiving millions of dollars in funding and critical acclaim even in its earliest stages. This
dream device is a system of ten synthetic organs that will be designed to mimic the organs of the
human body. The ultimate goal of the project is to engineer a device that can indicate what a
real human’s physiological response would be to any number of diseases, pharmaceuticals or
vaccines.
Key Words: human on a chip, organ on a chip, lab on a chip, microfabrication, tissue
engineering, drug testing, animal testing, microfluidics, chemical engineering, biology,
nanotechnology
Multimedia Suggestions:
Wyss Institute Interviews With Research Scientists ( http://wyss.harvard.edu/viewpage/293/ ).
This video contains several interviews with the scientists leading the human on a chip research
project. They provide insight into the human on a chip’s applications, and explain exactly why it
is such an exciting technology.
Wyss Institute Lung On A Chip Video ( http://wyss.harvard.edu/viewpage/240 ). This video
shows the way that the lung on a chip technology is fabricated, and one real-time demonstration
of its applications. The viewer need not be technical to understand the process of assembling the
lung on a chip described in this video.
Bio: Emma is a junior chemical engineer with an emphasis in nanotechnology. She does
biosensor research for the Armani Research Group. She is the Vice President for the USC
American Institute of Chemical Engineers and is on the Viterbi Engineering School's Presidents'
Council. In her free time she enjoys participating in Intervarsity Trojan Christian Fellowship and
exploring LA.
What a Wonderful World This Would Be
What if we could transform 1 year drug trials into 4 week drug trials? And what if we
could eliminate lab animals from the testing process completely? This is the future that the novel
human on a chip device can provide. It is an interconnected system of thumb-drive-sized
artificial organs that can mimic the behaviors of real human organs (see Figure 1). By mimicking
physiological responses of the entire human body, the human on a chip will be able to indicate
what a real human body’s response would be to a given drug or vaccine. It could truly change the
way we develop drugs and other human treatments [1].
Figure 1: Wyss Institute’s Lung On A Chip. The clear plastic portion is the “chip,” and the colored lines are a
system of micro-sized channels that mimic human organ functions. (source: http://spectrum.ieee.org/techtalk/biomedical/devices/how-to-build-a-human-on-a-chip)
Researchers from Harvard Wyss Institute for Biologically Inspired Engineering and MIT
(Massachusetts Institute for Technology) are hot on the trail to develop this useful technology.
DARPA (Defense Advanced Research Projects Agency, the central research agency for the US
Department of Defense), NIH (National Institutes of Health) and the FDA (Federal Drug
Administration) are hot on the trail to fund it. DARPA alone has pledged to contribute up to $37
million to the effort [1]. Based on this great volume of funding and support, we can see that the
human on a chip is not just a “fun” idea for engineers to experiment with. It truly has the power
to revolutionize the way we run drugs tests, develop pharmaceuticals, and even come up with
quick solutions in medical emergencies [2]. To complete this multimillion dollar project,
however, a diverse team of engineers are needed. The complex human on a chip system demands
not only doctors, but mechanical, chemical and electrical engineering expertise.
Conception and Development of Human on a Chip
With these exciting applications, the scientific world is eager to bring the human on a
chip to the marketplace. However, this cannot be done overnight. Over the past few decades,
researchers have perfected tissue engineering and microfabrication techniques, which are the two
underlying technologies needed to develop the human on a chip [3]. Because of the complex
inner-workings and components of the chip, it is clear that its assembly requires a wide range of
engineering and science disciplines. Biologists, pharmacists and medical doctors are needed to
design a system that truly mimics the human body. However, what way not be as evident is that
electrical and chemical engineers are also needed to fabricate and perfect the functionality of the
human on a chip’s microfluidic channels. Mechanical engineers and biomedical engineers will
also be needed for assembly and integration of all organs on a chip. The multidisciplinary team
and impressive lump of knowledge necessary to complete this project makes it quite the
engineering feat.
As one example of the multidisciplinary skills needed to create an organ on a chip,
consider the lung on a chip assembly and operation. Below is a cross section of the device.
Figure 2: Cross-sectional view of the lung on a chip channels, membrane and vacuums. (source:
http://news.harvard.edu/gazette/story/2012/11/new-way-to-model-human-disease/)
Scientists must first fabricate micrometer-scale channels for bodily fluids to flow (also
known as microfluidic channels) on a plastic substrate (the chip). They fabricate two adjacent
channels, one being the airway channel and the other being the blood channels. A flexible
membrane is then fabricated and oriented between the airway and blood channels. One side of
the membrane is lined with human airway lung cells, and the other wall is lined with human
capillary cells. This overall orientation is meant to represent the way that lung and blood vessel
cells are actually oriented in a human body’s lung air sac. Pumps and vacuums within these
small devices are also integrated in order to fully mimic the expansion and deflation of true
human lungs. A cross-sectional schematic of this device is shown in Figure 2. It is exciting to
note that scientists have had great success with testing the lung on a chip. They observed white
blood cells in the blood microchannel travel across the synthetic flexible membrane and
successfully attack harmful bacteria in the airway channel [4].
Similar to the lung on a chip, the gut on a chip will mimic the characteristics of a human
gut. It is designed on a silicon polymer chip, again about the size of a USB drive. The
researchers placed a layer of human intestinal cells on a flexible porous membrane, also very
similar to the lung on a chip’s membrane. For the gut on a chip system, the membrane is meant
to signifiy the intestinal barrier in actual human bodies that nutrients must pass through. Lastly, a
a vacuum is attached to the membrane. The vacuum helps promote the stretching and recoiling of
the gut on a chip system, mimicking the normal wave-like (peristaltic) movements that help
move food through a human’s digestive tract. Researchers hope to use this device in particular to
study common intestinal disorders such as Crohn’s disease and ulcerative colitis. In addition,
scientists can also use the gut on a chip to test possible treatments for the aforementioned
disorders, observing and recording how effective they are in curing a diseased gut on a chip
device [5]. The gut on a chip can be seen in Figure 3. Evidently, its macro-scale appearance is
very similar to the lung on a chip’s appearance.
Figure 3: Gut on a chip. As can be seen, the chip is no larger than the size of the human finger. (source:
http://spectrum.ieee.org/tech-talk/biomedical/devices/how-to-build-a-human-on-a-chip)
Once designed, all organs on a chip will follow a similar pattern of mimicking the organs
of the human body. The gut on a chip and lung on a chip have already been made, and Wyss
Institute researchers are hard at work on the spleen [5,6]. The ultimate goal is ten working organs
on a chip, all interconnected and functioning like a human body system. The intuitive system that
Wyss Institute researchers are aiming for can be easily understood by a non-technical audience.
The heart on a chip will beat, and be connected to a breathing lung. The spleen will filter blood.
The entire system will be connected by micro-sized channels of blood surrogate, just like the
human body has blood veins [7].
Applications
Engineers and businessmen are particularly interested in this technology because it will
likely prove to be a more time-efficient, facile and reliable tool for drug and vaccine testing as
opposed to current techniques such as lab animals. Yes, animal lovers can rejoice. The human on
a chip is a viable alternative [1]. Although animal subjects can be helpful in determining whether
a drug will be harmful to a human, our systems do not work the exact same way as theirs.
Animals do not always contract the same diseases that we do [5]. Professor Linda Griffith, one
of the head researchers of the MIT group, provides an excellent analogy to help us understand
why animal testing is not as reliable as the human on a chip. She says that if you put her in a cold
room, she will get cold and distracted easily. Her husband on the other hand will flourish and his
productivity will go up. It is the same for lab rats—some are simply more sensitive than others.
This is why a human on a chip would be a much better drug and vaccine tester. Each device
would function the same way and be highly predictable. Additionally, since the human on a chip
is designed with real human cells, it can much better mimic human physiological responses [8].
In addition to being a more reliable tool for drug testing, the human on a chip will also be
easy to monitor and observe because of its translucency [9]. If scientists insert a drug into the
human on a chip system, they can literally watch it travel through each organ and see how a
treatment adversely or positively affects the system. Dr. Don Ingber, one of the head researchers
on the human on a chip project, describes the path a drug might travel in clear detail. He says
that “you might deliver an oral drug to the gut, see it absorbed, watch it metabolize by the liver.
It’s being peed out by the kidney, and you’re looking for its toxicity on the heart” [7].
Not only is the human on a chip easy to monitor, but it will also be easy to use. The
researchers developing the human on a chip aim to make the training for their product quick and
painless, and the pricing relatively cheap. For example, they hope that biochemists can
incorporate a human on a chip device into their laboratory. This way, they can easily test out the
toxicity of a new biochemical they develop. All the chemist would have to do is administer a
small amount of the biochemical to the human on a chip system and then record the changes and
effects that the biochemical imparts on the human on a chip system [10].
Moving Quickly
Since all parties involved in the creation of the human chip desire to see this technology
implemented and manufactured on a large scale, the FDA will undoubtedly need to play a role in
its implementation. Surprisingly, even though the human on a chip is in relatively early research
stages, the FDA is already getting involved! The FDA is partnering with both DARPA and NIH
to get the human on a chip project completed. Their ultimate goal is, of course, to deliver
important treatments to patients and be assured that these treatments are safe. The FDA’s Chief
Scientist and Deputy Commissioner for Science and Public Health, Dr. Jesse Goodman, has
made very optimistic comments about the human on a chip. He hopes that the human on a chip
will be better at testing the toxicity of drugs, and therefore a superior alternative to lab animals.
Dr. Goodman points out that toxicity has specifically caused a great number of challenges for
researchers trying to develop medical products. The improved toxicity measurements that the
human on a chip provides fall under one of the FDA’s “Eight Science Priority Areas.” Simply
put, these are the eight critical research areas that the FDA believes must be improved. The
improvement in toxicity testing that the human on a chip may provide is crucial for the FDA’s
regulatory procedures to stay up to par and adequately serve the nation [11,12].
The Future
Before the human on a chip system can be implemented on a large scale for applications
such as what the FDA desires, researchers must overcome a great number of hurdles. First, they
must learn how to design all ten organs on a chip. The human on a chip will then go through
rigorous tests to determine its reliability and durability. The millions of dollars in funding on this
project will help the research groups complete their projects in a timely manner. However, they
do not have an estimated date of completion.
References
[1] E. Strickland. (2012, July 24). “How to Build a "Human-on-a-Chip.” IEEE Spectrum.
[Online]. Available: http://spectrum.ieee.org/tech-talk/biomedical/devices/how-to-build-ahuman-on-a-chip
[2] M. McCarthy. (2012, July 26). “Harvard gets $37M to develop 'human-on-a-chip' tech.”
Boston Business Journal. [Online]. Available: http://www.bizjournals.com/boston/blog/masshigh-tech/2012/07/harvard-gets-37m-to-develop-human-on-a-chip.html
[3] Khetani,et al. "Microscale Culture of Human Liver Cells for Drug Development." Nature
biotechnology, vol. 26, pp. 120-126, 2008.
[4] Wyss Institute. (2013, January 29). “Lung On A Chip.” Wyss Institute. [Online]. Available:
http://wyss.harvard.edu/viewpage/240
[5] J. Fang. (2012, March 28). “Gut-on-a-chip could replace animals in drug testing.”
Smartplanet. [Online]. Available: http://www.smartplanet.com/blog/rethinking-healthcare/guton-a-chip-could-replace-animals-in-drug-testing/8360
[6] B. Coxworth. (2013, April 9). “Spleen-on-a-chip could treat bloodstream infections.”
Gizmag. [Online]. Available: http://www.gizmag.com/spleen-on-a-chip-blood-filter/26994/
[7] K. Drummond. (2012, July 28). “Military's 'Body-on-a-Chip' Could Fast-Track
Pharmaceuticals.” Forbes. [Online]. Available:
http://www.forbes.com/sites/katiedrummond/2012/07/31/body-on-chip/
[8] B. Johnson. “The ‘Human Body on a Chip’ Project That Could Change Biological Warfare
and Medicine.” Slate. [Online]. Available:
http://www.slate.com/blogs/future_tense/2012/07/27/human_body_on_a_chip_from_mit_and_da
rpa_could_change_biological_warfare_medicine_.html
[9] Anonymous. “Human Lung on a Chip.” Journal of College Science Teaching, vol. 40, p. 14.
2010.
[10] Wyss Institute. “Organs on a Chip.” Wyss Institute. [Online]. Available:
http://wyss.harvard.edu/viewpage/293/
[11] “Science Priority Areas.” FDA. [Online]. Available:
http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm268110.htm
[12] FDA_Voice. “FDA Voice Interviews Jesse Goodman, M.D., M.P.H., on the DARPA and
NIH Project Collaboration: Human on a Chip.” FDA Voice. [Online]. Available:
http://blogs.fda.gov/fdavoice/index.php/tag/human-on-a-chip/