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futurity_medicine 00012.txt

#Paper circuit might diagnose Ebola in the field The first case of the Ebola outbreak currently ravaging West Africa appeared in Guinea in December 2013. But it wasn t until March 22 2014 that scientists finally confirmed the virus as Ebola. By that point 49 people had died already. Why did it take so long? Partly because confirming the diagnosis required that epidemiologists fly from Europe to Africa collect blood samples fly back to Europe and analyze them in sophisticated labs. Now a team of biologists has created a new tool that could provide a quick cheap way to perform sophisticated lab analyses and diagnostics in the field and may also offer a way to speed science in the lab. The tool called a paper gene circuit takes biological reactions out of cells and puts them onto a piece of paper. It is described in the journalâ#Cell.####This could really be a game-changer for a lot of applications including diagnostics##say James Collins who is a professor of biomedical engineering and medicine at Boston University and a core faculty member at Harvard s Wyss Institute.####You can literally carry this in your pocket and run an experiment in the field without any additional equipment.####The best diagnostic tools currently use antibodies to sense things like hormones or viruses in a patient s bloodstream. A standard pregnancy test for example tests for a hormone produced when a fertilized egg implants into a women s uterus. Such tests work well but can be expensive and time-consuming to develop.####The antibody-based tests are exquisitely sensitive and we can t compete with that sensitivity yet##says Keith Pardee a postdoctoral fellow in Collins lab coauthor of the Cell paper and a Wyss Institute research scientist.####But to make a custom antibody it costs between $4000 and $30000 and it will take between four and six months.####We made 24 different Ebola sensors and tested them in a day for $21 each.####The portable Ebola diagnostic is a proof-of-concept project not yet ready for the field. But it demonstrates the power of synthetic##gene circuits##made sterile portable and convenient. Like computer circuits gene circuits usually consist of a sensing component (or##input##)a logic gate and an output but they are crafted from parts of cells rather than wires and transistors. Over the past 15 years biologists have created hundreds of these gene circuits picking and choosing useful bits of biology and putting them together in new ways. Pardee s circuits use a device called a##toehold switch##created by coauthor Alexander Green also a postdoctoral fellow at Boston and Pardee s colleague at the Wyss Institute which allows the scientists to rationally design sensors and detectors. Because biological systems are particularly good at sensing changes in the environmentâ##our cells constantly monitor blood sugar and scan for infection for exampleâ##synthetic gene circuits are especially useful for detecting things like contaminants pesticides heavy metals and counterfeit drugs.####You can imagine that there s a lot of potential for these gene circuits because they can sense and they can report by say changing color. Does your fruit have listeria on it? is contaminated the soil with pesticides? The gene circuits can answer these questions##says Pardee. But there s a problem. Because synthetic gene circuits are usually hosted in organisms like E coli they can t be used for many applicationsâ##smearing fruit with E coli may detect contamination for example but will also add to it.####For these types of applications it s totally inappropriate##says Pardee.####We recognized that there was this potential but also this huge limitation.####Pardee wondered if there was a way to build a gene circuit that could function outside a cell. Ideally it would be transported sterile easily and stored without refrigeration and it would produce answers by changing color so a person could read the answer by eye alone. Pardee decided to try embedding the gene circuits and the necessary cellular enzymes into paper. In concept the idea is similar to ph stripsâ##a chemical reaction embedded into paper that changes color when it touches an acid or a base. But would something that worked for a chemical reaction work for biology too?####That was our first question: can we even get gene expression in paper?####says Pardee. Using a standard laser printer stocked with special wax-based inks he printed patterns of small dots onto uncoated filter paper. Each dot served as a well or pit to hold a gene circuit and the cellular enzymes that made it work. But Pardee wanted to take it a step further stabilizing the components at room temperature by freeze-drying them sticking them onto paper then seeing if he could add water and make them work again.####Freeze-drying is a pretty common thing to do in pharmaceuticals. If you freeze-dry a protein like insulin you can often re-constitute it and get its function back##says Pardee. But Pardee didn t know if he could freeze-dry the whole packageâ##the gene circuit instructions the enzymes that power the reactions the cellular machinery that builds proteinsâ##then add water and have it pop back to its former self.####If even one part didn t work then you d be stuck. That would be the weakest link##says Pardee.####But they all did! I was surprised. I immediately knew this was going to be really awesome.####Even better the paper circuits still worked after a year on the shelf.####There s still tons of work to do##he adds.####But I knew that having that core insight was going to enable the whole thing.#####This was Keith s big insightâ##freeze-drying the circuit##says Collins.##I couldn t believe it worked as well as it did. We got phenomenal activityâ##there was basically no loss of function.####Collins and Pardee are now working on technologies that will increase the sensitivity of the tool to make it practical for both diagnostics in the field and also for faster science in the lab.##In biology you spend a lot of time tool building. You build your tool then you do your experiment then you go back to building tools##says Pardee.####Now researchers can see if a tool works on paper in a matter of minutes and use only the best-performing tools in their experiment.####The technology can be embedded in any porous material such as cloth potentially opening the door for wider applications says Collins. He envisions smart scrubs for health care workers that can sense exposure to a virus; bandages that signal when a wound is infected with antibiotic-resistant bacteria; or smart clothing that tells a runner she s getting dehydrated.####This opens a lot of possibilities##says Collins.##It could give people a lot of valuable information very quickly.####Source: Boston Universit a

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