Wyss Institute develops prototype Ebola test in less than 12 hours with $20 in materials, perhaps paving the way for inexpensive paper-based diagnostic tests with a wide range of applications outside the medical laboratory

One goal of many synthetic biology researchers is to create in vitro diagnostic testing systems that produce results that are as accurate as those produced in today’s state-of-the-art clinical laboratories, yet are much cheaper to run because they incorporate low-cost materials, such as paper.

Recently, two teams of researchers worked to demonstrate how several synthetic biology methods, when combined with programmable paper-based diagnostic platform, could detect antibiotic-resistant bacteria and strain-specific Ebola virus. These findings were published in a peer-reviewed medical journal last fall.

Such cell-free circuits embedded in paper could be the breakthrough in synthetic biology that leads to pocketsize blotter tests that can detect such diseases as Ebola in the field.  Should this line of research be applied to clinical settings, pathologists and medical laboratory scientists could soon be processing bandages that change colors in the presence of certain bacteria, or examining paper-based clothing infused with diagnostic laboratory tests that react to bio-markers specific to a chronic disease patient’s condition.

Synthetic Biology Outside of the Clinical Laboratory

Researchers at Wyss Institute for Biologically Inspired Engineering at Harvard University have created a paper-based system that harnesses the genetic machinery of cells and embeds them into the fiber matrix of paper, which is then freeze dried, a process that allows for easy storage and transport.

“We can now take synthetic biology out of the lab and use it anywhere to better understand our health and environment,” said Wyss Postdoctoral Fellow Keith Pardee, Ph.D., in a Wyss Institute news release.

Keith Pardee, Ph.D

“In the protocols we’ve included in the article, researchers can immediately start to adopt this method to applications in their lab,” said Wyss Institute Postdoctoral Fellow Keith Pardee, Ph.D., about the latest advances in paper-based genetic testing, which are described in two papers published in the journal Cell. (Photo copyright Wyss Institute.)

Pardee and the other researchers published their findings in the November 4, 2014, issue of the journal Cell. The article titled “Paper-Based Synthetic Gene Networks,” details the paper-based platform for synthetic biology. In the paper’s summary, Pardee describes their pocket-sized paper diagnostic tool as an “alternate, versatile venue for synthetic biologists to operate and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab.”

New Delivery Method for Existing Paper-based Diagnostics

Their innovation could lay the foundation for inexpensive and highly scalable paper-based diagnostic tests covering a wide range of applications. While the idea of inexpensive paper-based diagnostics is not new—the first home pregnancy test, for example, was marketed in 1978—Pardee and his colleagues were able to demonstrate a method for embedding diverse gene circuits in paper using a freeze-drying method. The paper-based test they designed is safe at room temperature and maintains its effectiveness for up to a year. To be activated, the paper is rehydrated with water.

Circuits with colorimetric outputs display results. The group’s prototype Ebola test was developed in less than 12 hours and at a cost of $20 in materials, the BBC.com reports.

“This gives us a programmable sensor that can be readily and rapidly designed,” Boston University Biomedical Engineering Professor James Collins, Ph.D., who headed the Wyss Institute research team, told the BBC. “In a period of 12 hours, two of my team managed to develop 24 sensors that would detect different regions of the Ebola genome, and discriminate between the Sudan and the Zaire strains.”

Wyss Institute Faculty Portraits

James Collins, Ph.D., Biomedical Engineering Professor at Boston University, led researchers at Harvard University’s Wyss Institute for Biologically Inspired Engineering in developing a pioneering paper-based synthetic gene network that could lead to inexpensive clinical laboratory tests for diseases such as Ebola and other applications. “This is one of our biggest breakthroughs, one that I hope will have a positive impact, improving the lives of individuals worldwide,” Collins told Newsweek. (Photo copyright Wyss Institute)

Collins, whose previous research in 2000 showed genetic circuits could be created in a similar fashion to electronic circuits, said in a Newsweek article, “This is one of our biggest breakthroughs, one that I hope will have a positive impact, improving the lives of individuals worldwide.”

Collins credits the cross-team collaboration between his team at the Wyss Institute and that of Peng Yin, Ph.D., Associate Professor of Systems Biology at Harvard Medical School and a Wyss Core Faculty Member, with producing the synergy needed to develop this new diagnostic system.

Opportunities for Medical Laboratory Scientists

Clinical laboratory scientists do not have to wait to begin putting these innovations to use in their own labs. Pardee says the Wyss Institute’s paper-based diagnostic system can be replicated by following the steps outlined in their Cell article.

“In the protocols we’ve included in the article, researchers can immediately start to adopt this method to applications in their lab,” said Pardee in a Kurzweil Accelerating Intelligence article.

Consumer Products as Clinical Lab Tests

Technological innovations increasingly are paving the way for consumer products that serve double duty as clinical laboratory tests. Dark Daily previously has reported on Pixie Scientific’s “Smart Diaper,” which uses a panel of colored squares embedded with dry reagents (similar to the colored urine dipsticks patients commonly used in physicians’ offices), to alert parents to health changes such as a urinary tract infection, dehydration, or developing kidney problems (see Dark Daily “New ‘Smart Diaper’ Tests Baby’s Urine for Urinary Tract Infections, Dehydration, and Kidney Problems—Then Alerts Baby’s Doctor,” December 2, 2013.) This product is still not available for sale in the United States.

What experts find interesting about the work of Collins and Pardee and how they developed their diagnostic test for Ebola is how it combines different aspects of synthetic biology for the express purpose of generating diagnostic information. As noted in the press release, “The Ebola sensor was created by using the paper–based method and utilized a novel gene regulator called a ‘toehold switch,’ a new system for gene expression control with unparalleled programmability and flexibility reported in the second study in Cell. Although its inventors had designed the toehold switch to regulate genes inside living cells, its function was easily transferred to the convenience of ordinary freeze–dried paper, showcasing the true robustness of both the freeze–dried paper technique and the toehold switch.”

The press release further stated: “By combining forces, the two Wyss Institute teams showed that the toehold switch, so effective in living cells for its dynamic control of in vivo gene expression, is also fully capable of functioning in vitro on freeze–dried paper. With its impressive gene regulation functions able to be transported out of the lab for easy delivery of diagnostics and gene therapies, paper–based toehold switches promise a profound impact on human and environmental health.”

Another aspect of the collaboration of Collins and Pardee that will catch the attention of pathologists and clinical laboratory managers is the speed with which they created their paper-based diagnostic test for strain-specific Ebola. They report that it took them less than one day to create the test, which differentiates the Sudan and Zaire types of virus in about one hour. This shows how synthetic biology may be the field of science that eventually would allow diagnostic test developers to create new assays in very short periods of time.

—Andrea Downing Peck

Related Information:

Paper-Based Synthetic Gene Networks

Toehold Switches: De-Novo-Designed Regulators of Gene Expression

Prototype Paper Test Can Detect Ebola Strains

New Pocket-Sized Blotter Test Can Detect Ebola Strains in Just 30 Minutes

Synthetic Biology Looks Good on Paper

Synthetic Biology on Ordinary Paper; A New Operating System

Synthetic Biologists Create Paper-Based Diagnostic for Ebola

Synthetic Biology on Ordinary Paper, Results Off the Page

Bringing Synthetic Biology to (Freeze-dried) Paper

New ‘Smart Diaper’ Tests Baby’s Urine for Urinary Tract Infections, Dehydration, and Kidney Problems – Then Alerts Baby’s Doctor