Wyss Institute Can Identify Ebola Virus on Dry Paper Test Slips

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Wyss Institute, image by Harvard University
Wyss Institute, image by Harvard University

 

Harvard University’s Wyss Institute Announces Paper-Based Gene Detection Test Prototype, Which Can Identify Presence of Pathogens like the Ebola Virus

You may recall that last week we focused on biological and chemical laboratory analysis during our visit to the Gulf Coast Conference in Galveston. That event was a marked change from the scene here at McCormick Place in Chicago, where leading manufacturing and engineering technology is on display. But should we really think of biological laboratory science as being completely independent from engineering and manufacturing disciplines? The Wyss Institute for Biologically Inspired Engineering at Harvard University says no! If you haven’t heard of the Wyss Institute, you probably will this week, as they have announced a deceptively simple prototype of the paper-based synthetic gene detection system. Among its many potential uses, it can reportedly identify presence of the Ebola virus in an hour or less. It’s a pretty ingenious concept. So we have to ask what is different about the Wyss Institute and its approach to laboratory science?

 

The Wyss Institute Vision: Nature-Inspired Approach to Engineering and Manufacturing

Wyss Institute Director, Dr Donald Ingber, has a very clear vision: he is driving a multidisciplinary approach. You can call it either a nature-and-biology-inspired approach to engineering and manufacturing, or (contrariwise) a disciplined engineering-and-manufacturing approach to biological laboratory science.

 

Traditional Drug Discovery Approaches Using a Combination of Cell Cultures in Petri Dishes and Animal Testing Models Is Not Delivering Results

What are the problems that they are trying to solve at the Wyss Institute? Well, there are quite a few. But one of Dr Ingber’s primary concerns is the inefficiency of traditional drug discovery methods. Dr Ingber notes that each year we’re spending more on drug discovery, but percentage-wise researchers are getting fewer and fewer viable, effective drugs out of the pipeline. Dr Ingber believes that the poor return on drug development investment dollars is due to a fundamentally flawed approach in the traditional drug research system. He notes that we rely too heavily on just two basic techniques: animal testing models and cell testing in petri dishes or plates.

 

Many Biological Processes Need Simulated Breathing, Bodily Motion, or Even a Heartbeat to Function

Geraldine Hamilton, Ph.D., Senior Staff Scientist at the Wyss Institute, explained the reasons that relying on animal testing models and cells cultivated in petri dishes is not sufficient at a TEDxBoston event held last year.

 

 

According to Hamilton, the problem with traditional animal testing models is fairly clear-cut. Many potential drug discoveries fail human testing because there is not a one-to-one correspondence between each of the human organs with those in the test animals. Hamilton gives an example of a potential life-saving drug which failed human trials due to a side effect.

Why wasn’t this discovered earlier in the process before expending millions of dollars? The reason is the animal model did not metabolize the prototype drug in the kidneys the way it did in humans, which led to an unexpected serious side effect. And what’s wrong with testing drug candidates on plates or in petri dishes? Hamilton explains that many biological processes in the body cannot be reproduced in a static bed of agar in a petri dish. The reason is that cells behave entirely differently in the presence of simulated breathing,  simulated heartbeats or simulated physical motions.

 

New Approach: Organ–on–a–Chip

The Wyss Institute’s solution to the problem is to build what they call an “organ-on-a-chip”. These prototype chips, which look more like printer cartridges, are engineered to simulate specific organ processes, such as the oxygen transfer function of individual cells in the lung. For example, in a lung simulation, a long flexible membrane is populated with a thin coating of human lung cells. The membrane is supported at its two long edges by flexible tubes, which can be inflated and deflated to simulate breathing. By creating a simplified engineering model of the lung, Wyss Institute scientists can simulate specific lung diseases, such as asthma.

 

Diagram of "Lung-on-a-Chip" designed by The Wyss Institute at Harvard University. Image courtesy Wyss Institute.
Diagram of “Lung-on-a-Chip” designed by The Wyss Institute at Harvard University. Image courtesy Wyss Institute.

 

 

End Goal: Simulate the Entire Body System with an Interconnected Set of Plug-And-Play Organ–on–a–Chip Cartridges

The next goal for this project is to simulate all the organs in the human body by re-creating each of them on individual chips. The result will be a new synthetic human model, which will provide the end-to-end simulation needed to test the efficacy of potential new drug discoveries. The Wyss Institute plans to take the chip analogy even further — by creating modular laboratory test equipment that allows research scientists to snap in (or ‘plug and play’) different test organs into the device, depending upon the experiment(s) that they wish to run.

 

Synthetic Gene Networks Open up Possibilities for Simulation and Testing

What’s the next step after simulating organs on a chip? Wyss Core Faculty Members James Collins, Ph.D., and Peng Yin, Ph.D. published a significant new paper in Cell magazine last week that points the way toward programmable bio-sensors printed on paper which can be used for diagnostics, such as testing for the presence of an Ebola Virus in a lab specimen.

 

Printing Freeze-Dried Synthetic Gene Networks on Paper Test Strips

Testing for Ebola virus is just one of the many possibilities that this new approach to synthetic biology may bring.  How does the underlying technology work?

Mechanism of the Toehold Switch

Wyss Institute scientists have embedded effective synthetic gene networks in pocket-sized slips of paper capable of identifying pathogens such as Ebola virus. Credit: Harvard's Wyss Institute
Wyss Institute scientists have embedded effective synthetic gene networks in pocket-sized slips of paper capable of identifying pathogens such as Ebola virus. Credit: Harvard’s Wyss Institute

The video explains the mechanism of the so-called Toehold Switch, which — in a broad sense — acts like a transistor in electronic circuit board. This biological switch can sense the presence of different genes and in response turn replication on or off. In the Ebola virus test case, presence of the virus unlocks the toehold switch; once the switch is open, an entirely different gene can begin replicating, signaling with easily visible color changes on the paper test strip. We all know the story how transistors have enabled computer revolution, thanks to their small size, low energy use, reliability and portability. These new synthetic biology switches under development offer the promise of a parallel revolution in programmable biology computing. The possibilities are endless. Congratulations to the researchers at the Wyss Institute.

 

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