tag:theconversation.com,2011:/id/topics/biosensors-19317/articlesBiosensors – The Conversation2023-08-10T20:00:31Ztag:theconversation.com,2011:article/2112012023-08-10T20:00:31Z2023-08-10T20:00:31ZGenetically engineered bacteria can detect cancer cells in a world-first experiment<figure><img src="https://images.theconversation.com/files/542040/original/file-20230809-28-ahhuk7.jpg?ixlib=rb-1.1.0&rect=122%2C14%2C1874%2C1107&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>As medical technology advances, many diseases could be detected, prevented and cured with cells, rather than pills.</p>
<p>This branch of medicine is called <a href="https://www.aabb.org/news-resources/resources/cellular-therapies/facts-about-cellular-therapies">cellular or cell therapy</a>. It’s already used in clinical practice in some situations, such as patients receiving faecal microbial transplants (“<a href="https://theconversation.com/poo-transplants-beyond-the-yuck-factor-what-works-what-doesnt-and-what-we-still-dont-know-82265">poo transplants</a>”) when they have a severe gastrointestinal infection, or a bone marrow transplant for treating blood cancer.</p>
<p>Using <a href="https://theconversation.com/the-synthetic-biology-revolution-is-now-heres-what-that-means-102399">synthetic biology</a>, we can also engineer new and improved cells that could help us manage various diseases. In a new study <a href="http://dx.doi.org/10.1126/science.adf3974">published today in Science</a>, my colleagues and I describe how we engineered bacteria to successfully detect cancer cells.</p>
<h2>Leveraging competent bacteria</h2>
<p>Our project started with a presentation by synthetic biologist Rob Cooper during our colleague Jeff Hasty’s weekly lab meeting at the University of California San Diego. Rob was studying genes and gene transfer in bacteria.</p>
<p>Genes are the fundamental unit of genetic inheritance. It’s the stuff that gives you your mother’s smile or your father’s eye colour.</p>
<p>Gene transfer (or inheritance) is the process by which genes are passed from one cell to another. They may be inherited vertically – when one cell replicates its DNA and divides into two separate cells. This is what happens in reproduction, and how <a href="https://theconversation.com/curious-kids-how-does-dna-affect-our-fingerprints-and-eye-colour-199225">children inherit DNA</a> from their parents.</p>
<p>Genes may also, however, be inherited horizontally – when DNA is passed between unrelated cells, outside of parent-to-offspring inheritance.</p>
<p>Horizontal gene transfer is quite common in the microbial world. Certain bacteria can salvage genes from cell-free DNA found in their immediate environment. This free-floating DNA is released when cells die. When bacteria hoover up cell-free DNA into their cells, it’s called natural competence.</p>
<p>So, competent bacteria can sample their nearby environment and, in doing so, acquire genes that may provide them with an advantage.</p>
<p>After Rob’s talk, we engaged in some frenzied speculation. If bacteria can take up DNA, and cancer is defined genetically by a change in its DNA, then, theoretically, bacteria could be engineered to detect cancer.</p>
<p>Colorectal cancer seemed a logical proof of concept as the bowel is not just full of microbes, but is also full of tumour DNA when it’s struck by cancer.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/one-test-to-diagnose-them-all-researchers-exploit-cancers-unique-dna-signature-108078">One test to diagnose them all: researchers exploit cancers' unique DNA signature</a>
</strong>
</em>
</p>
<hr>
<h2>We put the bacterium through its paces</h2>
<p><em>Acinetobacter baylyi</em>, a naturally competent bacterium, was chosen to be the experimental biosensor – a disease-detecting cell.</p>
<p>Our team modified the <em>A. baylyi</em> genome to contain long sequences of DNA to mirror the DNA found in a human cancer gene we were interested in capturing. These “complementary” DNA sequences functioned as sticky landing pads – when specific tumour DNA was taken up by the bacteria, it was more likely to integrate into the bacterial genome.</p>
<p>It was important to integrate – hold in place – the tumour DNA. In doing so, we could activate other integrated genes, in this case an antibiotic resistance gene, as a signal for the cancer being detected. </p>
<p>The signal would work as follows: if bacteria could be grown on antibiotic-laden culture plates, their antibiotic resistance gene was active. Therefore they had detected the cancer.</p>
<p>We conducted a series of experiments in which our new bacterial biosensors and tumour cells were brought together in increasingly complex systems.</p>
<p>Initially, we simply marinated the biosensor with purified tumour DNA. That is, we presented our biosensor with the exact DNA it was built to detect – and it worked. Next, we grew the biosensor alongside living tumour cells. Again, it detected the tumour DNA.</p>
<p>Ultimately, we delivered the biosensor into live mice that either did or did not have tumours. In a mouse model of colorectal cancer, we inject mouse colorectal cancer cells into the colon, using mouse colonoscopy.</p>
<p>Over several weeks, the mice that were injected with cancer cells develop tumours, while the mice that were not injected serve as the healthy comparison group. Our biosensor perfectly discriminated between mice with and without colorectal cancer.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/yS7sqiXegL4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<h2>CATCH’s promising start – but more testing is needed</h2>
<p>After these encouraging results, we engineered the bacteria even further. The biosensor can now tell apart single base pair changes within the tumour DNA, allowing for finely tuned precision in how it detects and targets the genes. We have named this technology CATCH: cellular assay for targeted, CRISPR-discriminated horizontal gene transfer.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
</strong>
</em>
</p>
<hr>
<p>CATCH holds great promise. This technology uses cell-free DNA as a new input for synthetic biological circuits, and thus for the detection of a range of different diseases, particularly infections and cancers.</p>
<p>However, it is not yet ready to be used in the clinic. We’re actively working on the next steps – to increase the efficiency of DNA detection, to more critically evaluate the performance of this biosensor compared to other diagnostic tests, and, of course, to ensure patient and environmental safety.</p>
<p>The most exciting aspect of cellular healthcare, however, is not in the mere detection of disease. A laboratory can do that. </p>
<p>But what a laboratory cannot do is pair the detection of disease (a diagnosis) with the cells actually responding to the disease with an appropriate treatment.</p>
<p>This means biosensors can be programmed so that a disease signal – in this case, a specific sequence of cell-free DNA – could trigger a specific biological therapy, directly at the spot where the disease is detected in real time.</p>
<hr>
<p><em>Acknowledgements: I am grateful to be part of this incredible team including Professor Jeff Hasty, Dr Rob Cooper, Associate Professor Susan Woods and Dr Josephine Wright.</em></p><img src="https://counter.theconversation.com/content/211201/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dan Worthley owns shares in GenCirq, a synthetic biology company focussed on cancer therapeutics.
This work was supported by an NHMRC ideas grant (2020555) awarded to Dan Worthley.
Dan Worthley is listed as an inventor on a provisional patent application, “Detection of Cancer Mutations”, filed by the University
of California San Diego with the US Patent and Trademark Office (Application No. 63/239,100).</span></em></p>A proof-of-concept study using bacteria shows cell therapy can detect tumours – and may one day be able to treat them.Dan Worthley, Gastroenterologist and cancer scientist, South Australian Health & Medical Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1942652022-12-01T15:21:49Z2022-12-01T15:21:49ZMini bio-devices could help TB patients stick to their treatments<figure><img src="https://images.theconversation.com/files/496953/original/file-20221123-12-8elsb5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Handheld devices like this one, used for testing blood sugar levels, could help TB patients monitor their own drug levels.</span> <span class="attribution"><span class="source">Andrey_Popov/Shutterstock</span></span></figcaption></figure><p>Imagine the scenario: you’ve been told you have a disease that will kill you. But, the doctor adds, your life can be saved if you diligently take your medication. Don’t skip a day, don’t skip a dosage. Soon, however, you discover that the medication has a slew of side effects, including a loss of appetite, fatigue, and nausea. So you do stop.</p>
<p>This process plays itself out every day among people who have been diagnosed with tuberculosis (TB). Treatment <a href="https://www.cdc.gov/tb/topic/treatment/tbdisease.htm#">lasts for months</a>. The adherence rate is low. Numbers are hard to come by. But one <a href="https://link.springer.com/article/10.1186/1471-2458-11-393">national survey</a> in China – which is among the <a href="https://www.who.int/china/health-topics/tuberculosis">30 high-burden</a> TB countries that account for 87% of the world’s estimated cases – showed that as many as 73% of TB patients had, at the time of the survey, interrupted or suspended treatment. </p>
<p>South Africa is another of those 30 high-burden countries. The <a href="https://www.nicd.ac.za/wp-content/uploads/2021/02/TB-Prevalence-survey-report_A4_SA_TPS-Short_Feb-2021.pdf">First National TB Prevalence Survey</a> of 2018 found a prevalence rate of around 737 per 100,000 people, among the highest in the world. Again, numbers are hard to determine, but <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410008/">one study</a> looking at co-infection between extensively drug-resistant tuberculosis (XDR-TB) and HIV found that only around 70% of patients stuck to the optimal six-month treatment.</p>
<p>This poses risks for the individual and for entire communities. It is associated with higher transmission rates, fatalities, soaring costs for TB treatment programmes as well as the development of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561400/">multi-drug resistant strains</a>.</p>
<p>Multiple approaches are being taken to improve adherence to medication. These include the use of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462706/">higher doses</a> of certain medications in the hope of reducing treatment duration, although <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462706/">side-effects</a> like hearing loss have been reported, as has the building up of resistance to drugs.</p>
<p>Building on the sequencing of the human genome and improved technologies to determine individual genetic variations, there has been a growing movement towards personalised or precision medicine and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297695/#">personalised treatment regimens</a>. This works on the premise that medical treatments, including those for TB, can be customised to an individual patient. Hurdles include the costs involved in making those technologies accessible, and understanding how to tailor treatments to each person. </p>
<p>In the case of TB, there are also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982531/">other factors</a> to consider, like variation in the disease-causing strain and individual drug-metabolising capacity.</p>
<p>That’s where <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elan.202060384?af=R">my work</a> comes in. I am working to develop technologies that can accurately and reliably calculate an individual’s drug-metabolising capacity by measuring the “leftover” drugs in the TB patient’s blood or urine samples. The method involves the use of enzyme-based biosensors – a device used to detect chemical or biological substances. A popular application for such devices is the rapid detection of glucose levels in diabetics.</p>
<p>The results from my tests are promising. They reflect what other scholars doing similar experiments around the world show: these enzymatic biosensors could soon (scientists don’t like timelines) become a crucial weapon in efforts to make it easier for TB patients to adhere to their treatments.</p>
<h2>Finding the right enzyme</h2>
<p>One element of my work is to determine the right enzyme, already present in the human body, to include in the biosensor and serve as an amplifier or enhancer.</p>
<p>Biosensors should not be confused with the devices in which they sit – like the portable finger-prick testing kits used by diabetics, for example. They are simply a part of those devices. </p>
<p>Biosensors are typically made up of an electronic part, namely the transducer, that converts energy from one form to another; and a biological element such as an enzyme or even an antibody that acts as the sensor. </p>
<p>The electrochemical sensor itself does most of the hard measuring work. Essentially, the biological recognition element (the enzyme or antibody) interacts with the chemical component that you are seeking to identify and track, while the biological response is converted into an electric signal by the transducer, giving essential measurements. The biological element – in our case, the enzyme – simply boosts the signal.</p>
<p>My go-to enzyme is called CYP3A4. It forms part of a group of enzymes named cytochrome 450 or CYP450, which are known to play a key part in the <a href="https://pubmed.ncbi.nlm.nih.gov/23333322/">absorption of drugs</a> – and not just TB drugs. Because these enzymes react with 50% of all prescribed medication, they serve as a useful detector of the drug’s presence in a sample. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/tb-prevention-has-relied-on-the-same-vaccine-for-100-years-its-time-for-innovation-164735">TB prevention has relied on the same vaccine for 100 years. It's time for innovation</a>
</strong>
</em>
</p>
<hr>
<p>What makes CYP3A4 so useful is that it reacts with all four of the first-line drugs used to treat TB: namely isoniazid, ethambutol, pyrazinamide and rifampicin. </p>
<p>For purposes of <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elan.202060384?af=R">my study</a>, I developed a sensor by modifying the surface of a working electrode with nanoparticles of a range of materials. The enzyme was then electrostatically applied to this electrode. The completed biosensor was then tested on my samples: synthetic urine and plasma spiked with the four drugs.</p>
<p>My results showed that the biosensor could detected the drug “remnants” in my samples with high levels (90% and above) of accuracy. </p>
<h2>Real-world value</h2>
<p>So, what would the value of such a biosensor be in the real world? For one thing, it could allow clinicians to gauge whether a patient is a fast or poor metaboliser of the medication. </p>
<p>Typically, fast metabolisers quickly absorb the drugs, and only small vestiges remain in a blood or urine sample. They are likely to have few side effects since their bodies would not allow a build-up of the drug in their systems. However, they may need to take medication more regularly to make up for this quick absorption. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-key-to-treating-tb-may-be-in-a-common-carbohydrate-what-we-know-so-far-188412">The key to treating TB may be in a common carbohydrate. What we know so far</a>
</strong>
</em>
</p>
<hr>
<p>Poor absorbers, on the other hand, do not process the drugs well enough to do much good. The drug then builds up in the body and can lead to adverse side effects. These patients may require lower or less regular dosages.</p>
<p>There is even the potential that such enzyme-based biosensors could be put in devices that patients can use on their own, much like diabetics use monitors to measure their glucose levels. People with TB can then then do the same, modifying their regimens based on the readings and their doctors’ guidance. </p>
<p>Such improved management can, ultimately, keep adherence rates from slipping – which is good news for TB patients, their communities and public health systems across the world.</p><img src="https://counter.theconversation.com/content/194265/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Candice Franke receives funding from the National Research Foundation of South Africa. </span></em></p>There are several reasons that TB patients don’t or can’t adhere to their treatment.Candice Franke, Lecturer, University of the Western CapeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1500502020-12-07T13:12:29Z2020-12-07T13:12:29ZHow sensors monitor and measure our bodies and the world around us<figure><img src="https://images.theconversation.com/files/372919/original/file-20201203-15-1mo985t.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3413%2C1880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Infrared sensors make it possible to measure a person's body temperature without touching the person's body.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/NotRealNews/5aa5b825758e40839e86bb21d97685c4/photo?Query=Infrared%20temperature%20thermometer&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=6&currentItemNo=1">AP Photo/LM Otero</a></span></figcaption></figure><p>Sensors are all around. They are in automatic doors, at cash registers, in doctors’ offices and hospitals. They are used inside the body and outside.</p>
<p>Sensors detect aspects of the physical world – matter, energy, force – similarly to a person’s or animal’s senses. But instead of translating the information into nerve impulses, sensors translate them into electrical signals. The signals can be stored, processed on a computer or displayed on a screen. They can be a current or voltage that is constant or varying with time. </p>
<p>Sensors answer many important questions such as <a href="https://auto.howstuffworks.com/car-driving-safety/safety-regulatory-devices/tire-pressure-monitoring-systems.htm">how well-inflated</a> are a car’s tires, whether ice is building up on an airplane’s wings, whether carbon monoxide is in the air and <a href="https://www.howequipmentworks.com/pulse_oximeter/">how much oxygen</a> is in your blood.</p>
<p>As an <a href="https://scholar.google.com/citations?user=JimDEDgAAAAJ&hl=en">electrical engineer</a>, I work with sensors all the time to monitor biological and environmental indicators such as glucose, heart rate and function, temperature and pH.</p>
<p>In the past few decades, sensors have moved from being relatively large, bulky instruments to small, inexpensive devices that are easy to carry around, build into things like phones, scatter around the environment or place on or inside someone.</p>
<p>[<em><a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=experts">Expertise in your inbox. Sign up for The Conversation’s newsletter and get expert takes on today’s news, every day.</a></em>]</p>
<h2>How sensors work</h2>
<p>The “thing” to be sensed can be anything in the physical environment that you can think of. It can be light, temperature, moisture, radiation, chemicals such as hydrogen peroxide or lead, biochemical substances such as glucose or DNA, or radio waves. </p>
<p>Light sensors use a device known as a <a href="https://www.electronicshub.org/photodiode-working-characteristics-applications/">photodiode</a> to turn light into an electrical current. Certain materials and molecules give off light when they interact with other substances or particles. For example, invisible radiation is absorbed by materials known as <a href="https://tickle.utk.edu/smrc/">scintillators to produce visible light</a>, which is then detected by a light sensor. This is how X-rays are used in today’s medical imaging.</p>
<p>Chemical reactions can produce a current, which can be used to make a sensor for <a href="https://science.howstuffworks.com/chemical-sensing-devices.htm">detecting one or more of the chemicals</a> involved in a reaction. Changes in material shape or vibration <a href="https://www.explainthatstuff.com/piezoelectricity.html">can also produce a current or voltage</a>, which can be used to sense pressure or acceleration. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a hand holds a small electronic device" src="https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/373172/original/file-20201205-13-1ddkj6h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The black square on the right side of this device is a sensor for high-energy waves like X-rays.</span>
<span class="attribution"><span class="source">Tickle College of Engineering/University of Tennessee</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>What makes a good sensor</h2>
<p>A good sensor must be able to, for example, tell the difference in voltage when measuring light of one intensity against light of another intensity. A good sensor also needs to ensure that vibrations, temperature changes and extremes and other environmental factors don’t affect its output. </p>
<p>A sensor’s output must increase by the same amount as an increase in the concentration of the thing being sensed. That is, if I double the concentration of glucose, for example, does my sensor output always double? Finally, the sensor output must give the same value over and over for the same input and have a fast response time. </p>
<p>Cost is also a concern, because if a sensor is expensive only a few people or corporations can use it. If a sensor is low cost, then it can be made available to everyone.</p>
<p>So a sensor is anything that can detect an aspect of the physical environment and turn it into useful information. This information can help make your everyday life easier or solve some of today’s most pressing health issues.</p><img src="https://counter.theconversation.com/content/150050/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicole McFarlane has received funding from NSF, DOE, and N5 Sensors/ARPA-E. She is a member ASEE and a senior member of IEEE.</span></em></p>Sensors are everywhere, from your phone to your medicine cabinet. Here’s how they turn events in the physical world into words and numbers.Nicole McFarlane, Associate Professor of Electrical Engineering, University of TennesseeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1481602020-10-22T12:22:55Z2020-10-22T12:22:55ZA tiny circular racetrack for light can rapidly detect single molecules<figure><img src="https://images.theconversation.com/files/364775/original/file-20201021-17-gwtpr6.jpg?ixlib=rb-1.1.0&rect=0%2C14%2C4928%2C3238&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Light is key to ultrasensitive chemical sensors.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cropped-hand-of-scientist-testing-chemicals-in-royalty-free-image/1029344608?adppopup=true">Kwanchai Lerttanapunyaporn/EyeEm via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>My <a href="https://wp.optics.arizona.edu/jsu/">Little Sensor Lab</a> at the University of Arizona develops ultrasensitive optical sensors for medical diagnostics, medical prognostics, environmental monitoring and basic science research. Our sensor technology identifies substances by shining light on samples and measuring the index of refraction, or how much light is slowed down when it passes through a material, which is different from one substance to another – say, water and a DNA molecule. </p>
<p>Our technology lets us detect extremely low concentrations of molecules down to one in a million trillion molecules, and can give results in under 30 seconds.</p>
<p>Ordinarily, index of refraction is too subtle to detect in a single molecule, but using a <a href="https://doi.org/10.1038/lsa.2016.1">technology we developed</a>, we can pass light through a sample thousands of times, which amplifies the change. This makes our sensor among the most sensitive in existence.</p>
<p>The device includes a tiny ring that light races around – 240,000 times in 40 nanoseconds, or billionths of a second. A liquid sample surrounds the sensor. Some of the light extends outside of the ring, where it interacts with the sample thousands of times.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscope image of a tapered cylinder with a disc on top of it" src="https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=515&fit=crop&dpr=1 600w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=515&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=515&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=647&fit=crop&dpr=1 754w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=647&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=647&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The single-molecule sensor, magnified 1,700 times in this image, is narrower than the diameter of the average human hair. Light races around the ring at the top.</span>
<span class="attribution"><span class="source">Little Sensor Lab, University of Arizona</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Unlike other very sensitive detection methods, ours is label-free, meaning that we don’t have to add any radioactive tags or fluorescent labels to identify what we are trying to detect. This means we don’t have to process our samples as much. </p>
<p>Because our sensor is so sensitive, we require only small amounts of a substance, which is useful both for reducing costs and in cases where reagents are difficult to obtain.</p>
<h2>Why it matters</h2>
<p>Some diseases, like cancer, can progress silently, avoiding detection until it’s too late. An ultrasensitive sensor could detect a disease before symptoms appear, letting health care providers treat the disease early, when it’s still curable. The sensor could also be used in a COVID-19 breath test.</p>
<p>Having a rapid and sensitive sensor can also enable monitoring of disease progression and can quantify the effect of different treatments. Our lab, for example, currently works on detecting low concentrations of biomolecules that indicate Alzheimer’s disease or cancer in blood, urine and saliva samples.</p>
<h2>Other research in this field</h2>
<p>Many other approaches require that you either <a href="https://www.scientist.com/2014/06/05/fluorescent-tags-innocent-bystanders/">fluorescently “tag”</a> the thing that you’re trying to detect or amplify DNA using a <a href="https://www.genome.gov/about-genomics/fact-sheets/Polymerase-Chain-Reaction-Fact-Sheet">polymerase chain reaction</a> (PCR). For instance, current COVID-19 testing requires you to choose between a rapid antigen test, which is not as accurate, or a PCR test, which is accurate but expensive and time-consuming. </p>
<p>Active areas of research in this field also include ways to improve sample delivery to the sensor, which can improve the response time and reduce the amount of the target substance needed for detection. Researchers are also working on methods to improve sensor selectivity, which means the sensor can better distinguish the target substance from other substances. This reduces false positives. </p>
<h2>What’s next</h2>
<p>This month, our lab received a $1.8 million grant from the National Institutes of Health to improve the sensor. The next step after demonstrating that our devices work in a research setting would be to move to clinical trials.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>In addition, we are continually improving our sensor to make it more sensitive and more selective. We are also working on using the sensor to make a portable, point-of-care medical diagnostic device that could be used for at-home care or given to an EMT in an ambulance or a soldier on a battlefield.</p><img src="https://counter.theconversation.com/content/148160/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Judith Su receives funding from the NIH, the NSF, the Defense Threat Reduction Agency (DTRA), the Gordon & Betty Moore Foundation, the Flinn Foundation, and the Arizona Alzheimer's Consortium. She also owns a financial stake in Femtorays Technologies which develops label-free molecular sensors.</span></em></p>An optical sensor that can detect individual molecules promises early detection of diseases and environmental contamination.Judith Su, Assistant Professor of Biomedical Engineering and Optical Sciences, University of ArizonaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1330402020-09-24T12:21:12Z2020-09-24T12:21:12ZDynamic tattoos promise to warn wearers of health threats<figure><img src="https://images.theconversation.com/files/359680/original/file-20200923-17-1hotilu.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6357%2C4902&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In the not-too-distant future, tattoos could become medical diagnostic devices as well as body art.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cropped-view-of-female-doctor-in-white-coat-with-royalty-free-image/918494936?adppopup=true">LightFieldStudios/iStock via Getty Images </a></span></figcaption></figure><p>In the sci-fi novel <a href="https://www.nealstephenson.com/the-diamond-age.html">“The Diamond Age”</a> by Neal Stephenson, body art has evolved into “constantly shifting mediatronic tattoos” – in-skin displays powered by nanotech robopigments. In the 25 years since the novel was published, nanotechnology has had time to catch up, and the sci-fi vision of dynamic tattoos is starting to become a reality. </p>
<p>The first examples of color-changing nanotech tattoos have been developed over the past few years, and they’re not just for body art. They have a biomedical purpose. Imagine a tattoo that alerts you to a health problem signaled by a change in your biochemistry, or to radiation exposure that could be dangerous to your health.</p>
<p>You can’t walk into a doctor’s office and get a dynamic tattoo yet, but they are on the way. Early proof-of-concept studies provide convincing evidence that tattoos can be engineered, not only to change color, but to sense and convey biomedical information, including the onset of cancer. </p>
<h2>Signaling biochemical changes</h2>
<p>In 2017, researchers tattooed pigskin, which had been removed from the pig, with <a href="http://doi.org/10.1145/3123021.3123039">molecular biosensors that use color</a> to indicate sodium, glucose or pH levels in the skin’s fluids.</p>
<p>In 2019, a team of researchers expanded on that study to include <a href="http://doi.org/10.1002/anie.201904416">protein sensing and developed smartphone readouts for the tattoos</a>. This year, they also showed that <a href="http://doi.org/10.1016/j.snb.2020.128378">electrolyte levels could be detected with fluorescent tattoo sensors</a>. </p>
<p>In 2018, a team of biologists developed a <a href="http://doi.org/10.1126/scitranslmed.aap8562">tattoo made of engineered skin cells</a> that darken when they sense an imbalance of calcium caused by certain cancers. They demonstrated the cancer-detecting tattoo in living mice. </p>
<h2>UV radiation sensors</h2>
<p><a href="https://www.emergentnanomaterials.com/">My lab</a> is <a href="https://go.ted.com/carsonbruns">looking at tech tattoos from a different angle</a>. We are interested in sensing external harms, such as ultraviolet radiation. UV exposure in sunlight and tanning beds is the main risk factor for all types of skin cancer. Nonmelanoma skin cancers are the most common malignancies in the U.S., Australia and Europe. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A four-panel series shows a UV-activated tattoo appearing in a star pattern, erased and then appearing in a dot pattern" src="https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=151&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=151&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=151&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=190&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=190&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358923/original/file-20200920-20-5f64p7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=190&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">UV-activated tattoo ink is invisible until exposed to UV light.</span>
<span class="attribution"><span class="source">Jesse Butterfield/The Laboratory for Emergent Nanomaterials, University of Colorado Boulder</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>To help address this problem, we developed <a href="https://doi.org/10.1021/acsnano.0c05723">an invisible tattoo ink that turns blue only in UV light</a>, alerting you when your skin needs protection. The tattoo ink contains a UV-activated dye inside of a plastic nanocapsule less than a micron in diameter – or thousandth of a millimeter – about the same size as an ordinary tattoo pigment.</p>
<p>The nanocapsule is needed to make the color-changing tattoo particles large enough. If tattoo pigments are too small, the immune system rapidly clears them from the skin and the tattoo disappears. They are implanted using tattoo machines in the same way as regular tattoos, but they last for only several months before they start to degrade from UV exposure and other natural processes and fade, requiring a “booster” tattoo. </p>
<p>I served as the first human test subject for these tattoos. I created “solar freckles” on my forearm – invisible spots that turned blue under UV exposure and reminded me when to wear sunscreen. My lab is also working on invisible UV-protective tattoos that would absorb UV light penetrating through the skin, like a long-lasting sunscreen just below the surface. We’re also working on “thermometer” tattoos using temperature-sensitive inks. Ultimately, we believe tattoo inks could be used to prevent and diagnose disease.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/4CGFPbFqdJ4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">In this TEDx talk, the author demonstrates the UV-detecting tattoo.</span></figcaption>
</figure>
<h2>Temporary high-tech tattoos</h2>
<p>Temporary transfer tattoos are also undergoing a high-tech revolution. <a href="http://doi.org/10.1126/science.1206157">Wearable electronic tattoos</a> that can sense electrophysiological signals like heart rate and brain activity or monitor hydration and glucose levels from sweat are under development. They can even be used for <a href="https://duoskin.media.mit.edu/">controlling mobile devices</a>, for example shuffling a music playlist at the touch of a tattoo, or for <a href="http://www.hybrid-ecologies.org/projects/12-skintillates">luminescent body art</a> that lights up the skin. </p>
<p>The advantage of these wearable tattoos is that they can use battery-powered electronics. The disadvantage is that they are much less permanent and comfortable than traditional tattoos. Likewise, electronic devices that go underneath the skin are being developed by <a href="https://doi.org/10.1063/1.3238552">scientists</a>, <a href="https://doi.org/10.1145/2207676.2207745">designers</a> and <a href="https://wiki.biohack.me/wiki/index.php?title=Modifications_-_Implantable_Mods">biohackers</a> alike, but they require invasive surgical procedures for implantation. </p>
<p>Tattoos injected into the skin offer the best of both worlds: minimally invasive, yet permanent and comfortable. New <a href="http://doi.org/10.1063/1.5074176">needle-free tattooing methods</a> that fire microscopic ink droplets into the skin are now in development. Once perfected they will make tattooing quicker and less painful. </p>
<h2>Ready for everyday use?</h2>
<p>The color-changing tattoos in development are also going to open the door to a new kind of dynamic body art. Now that tattoo colors can be changed by an electromagnetic signal, you’ll soon be able to “program” your tattoo’s design, or switch it on and off. You can proudly display your neck tattoo at the motorcycle rally and still have clear skin in the courtroom. </p>
<p>As researchers develop dynamic tattoos, they’ll need to study the safety of the high-tech inks. As it is, little is known about the safety of the more than 100 different pigments used in normal tattoo inks. The <a href="https://www.fda.gov/cosmetics/cosmetic-products/tattoos-permanent-makeup-fact-sheet">U.S. Food and Drug Administration</a> has not exercised regulatory authority over tattoo pigments, citing other competing public health priorities and a lack of evidence of safety problems with the pigments. So U.S. manufacturers can put whatever they want in tattoo inks and sell them without FDA approval. </p>
<p>So far, there is <a href="http://doi.org/10.1586/edm.09.28">no evidence that tattoos cause cancer</a>, and <a href="http://doi.org/10.1111/phpp.12181">one study even found that black tattoos protect against UV-induced skin cancer</a>. Still, many tattoo inks <a href="http://doi.org/10.1111/j.1600-0536.2007.01301.x">contain or degrade into substances that are known to be hazardous</a>, and health complications including infection, allergy and granuloma have been <a href="https://doi.org/10.1016/j.clindermatol.2007.05.012">found in about 2% of tattoos</a>. More research is needed to understand the long-term effects of nano- and microimplants in the skin in general. </p>
<p>A wave of high-tech tattoos is slowly upwelling, and it will probably keep rising for the foreseeable future. When it arrives, you can decide to surf or watch from the beach. If you do climb on board, you’ll be able to check your body temperature or UV exposure by simply glancing at one of your tattoos.</p><img src="https://counter.theconversation.com/content/133040/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Carson J. Bruns does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers are developing tattoo inks that do more than make pretty colors. Some can sense chemicals, temperature and UV radiation, setting the stage for tattoos that diagnose health problems.Carson J. Bruns, Assistant Professor, University of Colorado BoulderLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/952262018-05-06T20:11:20Z2018-05-06T20:11:20ZCustom-built DNA could be used as a sensor probe<figure><img src="https://images.theconversation.com/files/217430/original/file-20180503-153866-olqlo7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Imagine using synthetic DNA as a sensor recording device.</span> <span class="attribution"><span class="source">Rost/Shutterstock</span></span></figcaption></figure><p>Researchers believe that DNA – the molecule that stores information about life – could one day be used as a type of sensor, to record information based on its surroundings.</p>
<p>Synthetic DNA (not produced in an organism and not containing genetic information of a species) has already been <a href="https://www.zdnet.com/article/microsofts-dna-storage-breakthrough-could-pave-way-for-exabyte-drives/">used to store data</a>, as a sort of biological hard drive. </p>
<p>But now, <a href="http://science.sciencemag.org/content/360/6385/eaap8992">MIT researchers Weixin Tang and David Liu</a> say that their CAMERA system (acronym for CRISPR-mediated analogue multi-event recording apparatus) makes bacteria able to record their surroundings.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">What is CRISPR gene editing, and how does it work?</a>
</strong>
</em>
</p>
<hr>
<p>The microbes are able to sense and note in their DNA the presence or absence of sunlight, antibiotics, or nutrients in their vicinity.</p>
<p>This system has two variations. </p>
<p>CAMERA 1 records the presence and intensity of an external molecule by changing the ratio of two small circular DNA pieces (called plasmid) inside the bacteria. This allows you to determine whether, how much and for how long the microbe was sensing the external molecule. </p>
<p>CAMERA 2 is more advanced and records by making a DNA edit (imagine the equivalent of burning a DVD, but on the genome). </p>
<p>Both systems can keep the information records steady for several hours. And as a true recording device, it has a “reset” function that cleans the information and sets the system ready for another recording.</p>
<h2>How it works</h2>
<p>An audio or video recorder in effect translates information. The composition and complexity of photons and sound waves is transformed in a way possible to store. A reading device then retrieves that information.</p>
<p>The same principles apply to recording in DNA format, and in this case there are two technologies that make this possible. </p>
<p>The first one is <a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR/Cas9</a>, a gene editing tool. CRISPR can target DNA sequences very precisely. In CAMERA 1, CRISPR works by breaking down one of these two circular DNA pieces, changing their ratio.</p>
<p>CAMERA 2 uses CRISPR to make small changes to the original DNA sequence. When the molecule of interest is in the environment, it causes the cells to produce CRISPR in a controlled manner. In that way, the result is precise and tied closely to the external cue.</p>
<p>The second technology is DNA sequencing, and in particular <a href="https://www.youtube.com/watch?v=jFCD8Q6qSTM">next generation sequencing</a>. The information recorded needs to be retrieved and analysed. </p>
<p>That may sound straightforward, but keep in mind that we need to detect a few changes in a one or two letters out of the few million letters that make the bacterial genome.</p>
<p>Next generation sequencing allows reading DNA in very high speed and very high accuracy. More importantly, it makes the cost of reading DNA drop, making routine sequencing applications financially viable. </p>
<h2>What can we use it for?</h2>
<p>There are advantages of such a system compared to current sensors.</p>
<p>The applications on basic research are obvious. A recording device can store information about the history of a cell and tell us, for example, when a pathogen starts producing a toxin, or when the nutrients run low in a cell.</p>
<p>In order to answer such questions currently, we need to use either reporter genes, that require constant monitoring, or expensive and invasive metabolomics techniques.</p>
<p>The biggest application potential lies in micro-sensors. Specialised cells could monitor the concentrations of a varying of compounds. </p>
<p>The advantage to current chemical/electrical sensors is that biological systems are more versatile in monitoring and reacting to many compounds with high accuracy. As only a few molecules are needed for a successful recorder, bio-sensors can be smaller in size and record multiple signals at the same time. </p>
<h2>The next breakthrough</h2>
<p>In my opinion, a true breakthrough in the technology would be the development of a cell-free DNA recorder. </p>
<p>Recording in cells limits the recording environments to these that the cell can grow. A cell-free system, containing only the sensing molecules and the DNA-recording apparatus would have a number of advantages.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/storing-data-in-dna-brings-nature-into-the-digital-universe-78226">Storing data in DNA brings nature into the digital universe</a>
</strong>
</em>
</p>
<hr>
<p>The information would be easier to access and assess, as it would not be buried in the genome of the organism. The system would be simpler, thus easier to calibrate and optimise. Moreover there would be a reduced risk for contamination, as it would not contain a living organism and it would rely on fully synthetic DNA.</p>
<p>Synthetic biology <a href="https://cosmosmagazine.com/biology/life-2-0-inside-the-synthetic-biology-revolutionhttps:/cosmosmagazine.com/biology/life-2-0-inside-the-synthetic-biology-revolution">is promising to revolutionise biological research</a> and applications. These developments have become possible due to the reduced cost to read and write DNA. </p>
<p>I expect more and more creative uses of this fundamental molecule of life, and exciting applications in our everyday life.</p><img src="https://counter.theconversation.com/content/95226/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Konstantinos Vavitsas receives funding from the University of Queensland and CSIRO Synbio FSP platform. He is affiliated with the aforementioned organisations, he is member of the executive board of Synthetic Biology Australasia and community editor for PLOS Synbio. </span></em></p>One way to make sensors small is to make them out of something that’s incredibly small in the first place, such as DNA.Konstantinos Vavitsas, CSIRO Future Science Fellow in Synthetic Biology, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/856262017-10-22T11:11:59Z2017-10-22T11:11:59ZHow African elephants’ amazing sense of smell could save lives<figure><img src="https://images.theconversation.com/files/190996/original/file-20171019-1048-18eenfo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chishuru, a male African elephant, indicates a target scent during trials.</span> <span class="attribution"><span class="source">Graham Alexander</span></span></figcaption></figure><p>For 27 years Angola was gripped by <a href="http://www.sahistory.org.za/article/angolan-civil-war-1975-2002-brief-history">civil war</a>. Half a million human lives were lost and wildlife, too, was decimated to sustain troops. Rhino and elephants became valuable targets – rhino horn and ivory served as currency for arms among rebel forces. </p>
<p>During the conflict elephant populations fled across the border into Botswana, Zambia and the Democratic Republic of the Congo. When the war ended in 2002 animal populations slowly started to return to their pre-conflict grazing grounds. But a huge problem remained: <a href="http://www.news24.com/Africa/News/5m-landmines-buried-in-Angola-20020627">millions of landmines</a> were still <em>in situ</em> and <a href="https://www.halotrust.org/where-we-work/africa/angola/">undetonated across Angola</a>. Many elephants were <a href="http://www.sciencedirect.com/science/article/pii/S0168159115002063">killed and maimed</a> by the explosives as they attempted to recolonise.</p>
<p>Data collected from collared elephants moving through the affected areas <a href="http://news.nationalgeographic.com/news/2007/07/070716-elephants-mines_2.html">showed</a> herds avoiding minefields. This suggested that at least some of the returning elephants had associated minefields with danger. What could this association be based on? Had the minefield-avoiding elephants seen others killed in those areas? Or had they associated the smell of landmines with danger, extrapolating risk to other areas where the odour was present?</p>
<p>We couldn’t answer all these questions. To narrow down our search my colleagues and I set about finding out whether elephants could smell the main component of landmines – Trinitrotoluene (TNT). </p>
<p>TNT has a low volatility – the ease at which a substance moves into the air column. This makes it difficult to detect using smell. But some animals are excellent landmine sniffers – among them dogs and <a href="http://news.nationalgeographic.com/2015/10/151006-giant-rats-landmines-cambodia-science-animals/">Gambian Pouched Rats</a>. <a href="http://news.nationalgeographic.com/news/2004/02/0210_040210_minerats.html">Bees</a> are also good at it. </p>
<h2>Genetic aspect</h2>
<p>What gives an animal a wide sense of smell comes down to how many different kinds of olfactory receptors it has, and this is determined by the species’ genes. </p>
<p>African elephants have more than double the <a href="http://genome.cshlp.org/content/24/9/1485.short">number of genes</a> associated with olfactory reception compared with dogs: about 2000 versus dogs’ 811. This suggests that olfaction must play an enormous role in elephants’ lives. In fact, elephants have the <a href="https://voices.nationalgeographic.org/2014/07/22/animals-elephants-smell-trunks-genes-africa-science/">highest count</a> of any species tested to date, meaning that they could quite possibly be the best smellers in the animal kingdom. </p>
<p>Not only were we eager to find out whether they could detect TNT using olfaction, but also how their abilities compared to those of highly trained, TNT-detection dogs.</p>
<p>To do this, we enlisted the help of three African elephants at “<a href="http://adventureswithelephants.com/">Adventures With Elephants</a>” – an educational tourism facility focused on raising awareness about conservation. Using reward-based training techniques, we trained the elephants to indicate whenever they could smell TNT among a lineup of blank, non-smelly samples initially and then later, highly volatile distractor odours. </p>
<p>Samples were individual filter papers loaded with trace amounts of one of the following odours: TNT; petroleum; acetone; bleach; detergent; tea; or nothing at all (blanks). These filter papers, or samples, were placed individually into a bucket, and sample buckets (eight in total) were placed 6 metres apart, in a straight line. The elephants were trained to walk along the line and investigate each bucket, raising their front leg and waving it over the selected bucket whenever they thought they could smell TNT. </p>
<figure>
<iframe src="https://player.vimeo.com/video/238896128" width="500" height="281" frameborder="0" webkitallowfullscreen="" mozallowfullscreen="" allowfullscreen=""></iframe>
<figcaption><span class="caption">Mussina, a female African elephant, is put through her TNT-sniffing paces.</span></figcaption>
</figure>
<p>The results suggest that elephants are <a href="https://www.researchgate.net/publication/279888080_Biological_detection_of_explosives">even better</a> at one aspect of the sniffing process than <a href="https://www.researchgate.net/publication/279888080_Biological_detection_of_explosives">dogs</a>, the animals currently considered the gold standard in landmine detection.</p>
<h2>Sensitivity and selectivity</h2>
<p>Two metrics, sensitivity and selectivity, are incredibly important in detection science. Measures of these allow researchers to understand how well a biodetector such as a dog or elephant is performing. They also allow for comparisons across species. </p>
<p>The elephants missed only one out of 97 TNT samples during our trials. This translated into a phenomenal sensitivity score of 99.7%. Sensitivity is the propensity to indicate whenever a target substance (in this case TNT) is present. In comparison, sensitivity scores for TNT-detection dogs have been reported as 93.7%.</p>
<p>The elephants only made six false-positive indications, mistaking five out of 53 acetone samples and one out of 24 petrol samples for TNT. This incredibly low frequency of false-positives resulted in a respectable selectivity score – that is, the propensity to only indicate TNT, and not just any odourous substance – of 95.1%. This is a bit shy of the 100% score reported for dogs.</p>
<p>Our findings indicate that elephants are almost 5% more likely than dogs to indicate the presence of TNT when, in fact, there is none. But dogs are almost 6% more likely to miss TNT than elephants are. It’s obviously better for TNT detectors to be prone to false positives rather than false negatives: in fact it could be the difference between life and death. </p>
<h2>Real world application</h2>
<p>So does this mean that elephants should take over TNT-sniffing dogs’ duties? </p>
<p>No, absolutely not. We have no intention of putting elephants in harm’s way: their sheer size and weight makes them completely unsuited to being infield TNT detectors.</p>
<p>But remote elephant teams could act as valuable support to current demining operations in countries like Angola. </p>
<p>Samples collected via <a href="https://www.gichd.org/resources/publications/detail/publication/remote-explosive-scent-tracing-rest/#.Wd9xLFuCzIU">Remote Explosive Scent Tracing</a> by unmanned vehicles such as drones could be sent to the elephants for screening. The information gathered from TNT-detection elephants could be passed on to demining teams working at the front lines, even before they are deployed. This early warning system could potentially save the lives of the deminers and their dedicated biosensor companions.</p>
<h2>Other areas to explore</h2>
<p>Elephants’ ability to correctly identify and discriminate a learned scent from other odours suggests that they may also be useful in other biosensor fields such as early disease detection.</p>
<p>Detection dogs are used in medical and biological settings. I have used them myself as a biologically-relevant model to demonstrate that <a href="https://theconversation.com/the-ultimate-in-stealth-puff-adders-employ-camouflage-at-every-level-53316">puff adders</a> are undetectable via olfaction. </p>
<p>Specially trained dogs already screen for cancers, diabetes, epilepsy, alien invasives, harmful microbes and pests. Some <a href="https://www.ncbi.nlm.nih.gov/pubmed/26863620">scent-matching dogs</a> are even able to match collected samples to individuals, forgoing the need for expensive and time-consuming genetic testing. The dogs’ performance in these fields is, in most cases, proving <a href="http://www.sciencedirect.com/science/article/pii/S0168159115002063">more reliable</a> than mechanical devices.</p>
<p>Elephants could rival dogs’ sensitivity abilities in these fields, as they did for TNT-detection. They require less maintenance training than dogs to keep them on the target scent. Our elephants were able to repeat the same tests with high success a year after their last trial, with no intervening maintenance training. </p>
<p>In addition, given their longevity – they can live to around <a href="https://www.sanbi.org/creature/african-elephant">60 years</a> in the wild – elephants, once trained, could serve as long-standing biosensors that far outlive any of their current biosensor counterparts.</p>
<p>And, importantly, biologically appropriate tasks that engage natural behaviours to gain reward is highly stimulating for captive animals. So not only could elephants potentially save lives while sniffing out danger – they could have fun at the same time.</p><img src="https://counter.theconversation.com/content/85626/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashadee Kay Miller received funding from the Army Research Office (ARO) for this work, and currently receives funding from the NRF, ARO and the U.S. Army Research, Development and Engineering Command for her research on chemical crypsis.</span></em></p>Elephants have the highest count of olfactory receptor genes of any species tested to date. This suggests that they may be the best smellers in the animal kingdom.Ashadee Kay Miller, PhD Candidate, School of Animal, Plant and Environmental Sciences, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/713062017-01-18T11:03:34Z2017-01-18T11:03:34ZUsing electricity, not molecules, to switch cells on and off<figure><img src="https://images.theconversation.com/files/153142/original/image-20170118-21179-14d7xry.jpg?ixlib=rb-1.1.0&rect=0%2C651%2C5000%2C3263&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Will your cellphone be able to communicate with bacteria in your body?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-depicting-viruses-bacteria-on-545224942">Bacteria image via www.shutterstock.com.</a></span></figcaption></figure><p>Microelectronics has transformed our lives. Cellphones, earbuds, pacemakers, defibrillators – all these and more rely on microelectronics’ very small electronic designs and components. Microelectronics has changed the way we collect, process and transmit information.</p>
<p>Such devices, however, rarely provide access to our biological world; there are technical gaps. We can’t simply connect our cellphones to our skin and expect to gain health information. For instance, is there an infection? What type of bacteria or virus is involved? We also can’t program the cellphone to make and deliver an antibiotic, even if we knew whether the pathogen was Staph or Strep. There’s a translation problem when you want the world of biology to communicate with the world of electronics.</p>
<p>The research we’ve just <a href="http://dx.doi.org/10.1038/ncomms14030">published with colleagues in Nature Communications</a> brings us one step closer to closing that communication gap. Rather than relying on the usual molecular signals, like hormones or nutrients, that control a cell’s gene expression, we created a synthetic “switching” system in bacterial cells that recognizes electrons instead. This new technology – a link between electrons and biology – may ultimately allow us to program our phones or other microelectronic devices to autonomously detect and treat disease. </p>
<h2>Communicating with electrons, not molecules</h2>
<p>One of the barriers scientists have encountered when trying to link microelectronic devices with biological systems has to do with information flow. In biology, almost all activity is made possible by the transfer of molecules like glucose, epinephrine, cholesterol and insulin signaling between cells and tissues. Infecting bacteria secrete molecular toxins and attach to our skin using molecular receptors. To treat an infection, we need to detect these molecules to identify the bacteria, discern their activities and determine how to best respond.</p>
<p>Microelectronic devices don’t process information with molecules. A microelectronic device typically has silicon, gold, chemicals like boron or phosphorus and an energy source that provides electrons. By themselves, they’re poorly suited to engage in molecular communication with living cells.</p>
<p>Free electrons don’t exist in biological systems so there’s almost no way to connect with microelectronics. There is, however, a small class of molecules that stably shuttle electrons. These are called “redox” molecules; they can transport electrons, sort of like wire does. The difference is that in wire, the electrons can flow freely to any location within; redox molecules must undergo chemical reactions – oxidation or reduction reactions – to “hand off” electrons.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/153119/original/image-20170117-21179-1xijm25.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bacteria are engineered to respond to a redox molecule activated by an electrode by creating an electrogenetic switch.</span>
<span class="attribution"><span class="source">Bentley and Payne</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Turning cells on and off</h2>
<p>Capitalizing on the electronic nature of redox molecules, we genetically engineered bacteria to respond to them. We focused on redox molecules that could be “programmed” by the electrode of a microelectronic device. The device toggles the molecule’s oxidation state – it’s either oxidized (loses an electron) or reduced (gains an electron). The electron is supplied by a typical energy source in electronics like a battery.</p>
<p>We wanted our bacteria cells to turn “on” and “off” due to the applied voltage – voltage that oxidized a naturally occurring redox molecule, pyocyanin.</p>
<p>Electrically oxidizing pyocyanin allowed us to control our engineered cells, turning them on or off so they would synthesize (or not) a fluorescent protein. We could rapidly identify what was happening in these cells because the protein emits a green hue. </p>
<p>In another example, we made bacteria that, when switched on, would swim from a stationary position. Bacteria normally swim in starts and stops referred to as a “run” or a “tumble.” The “run” ensures they move in a straight path. When they “tumble,” they essentially remain in a one spot. A protein called CheZ controls the “run” portion of bacteria’s swimming activity. Our electrogenetic switch turned on the synthesis of CheZ, so that the bacteria could move forward.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=408&fit=crop&dpr=1 600w, https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=408&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=408&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=513&fit=crop&dpr=1 754w, https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=513&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/153118/original/image-20170117-21179-5fal5y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=513&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bacteria can naturally join forces as biofilms and work together.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov">CDC/Janice Carr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We were also able to electrically signal a community of cells to exhibit collective behavior. We made cells with switches controlling the synthesis of a signaling molecule that diffuses to neighboring cells and, in turn, causes changes in their behavior. Electric current turned on cells that, in turn, “programmed” a natural biological signaling process to alter the behavior of nearby cells. We exploited bacterial quorum sensing – a natural process where bacterial cells “talk” to their neighbors and the collection of cells can behave in ways that benefit the entire community.</p>
<p>Perhaps even more interesting, our groups showed that we could both turn on gene expression and turn it off. By reversing the polarity on the electrode, the oxidized pyocyanin becomes reduced – its inactive form. Then, the cells that were turned on were engineered to quickly revert back to their original state. In this way, the group demonstrated the ability to cycle the electrically programmed behavior on and off, repeatedly.</p>
<p>Interestingly, the on and off switch enabled by pyocyanin was fairly weak. By including another redox molecule, ferricyanide, we found a way to amplify the entire system so that the gene expression was very strong, again on and off. The entire system was robust, repeatable and didn’t negatively affect the cells.</p>
<h2>Sensing and responding on a cellular level</h2>
<p>Armed with this advance, devices could potentially electrically stimulate bacteria to make therapeutics and deliver them to a site. For example, imagine swallowing a small microelectronic capsule that could record the presence of a pathogen in your GI tract and also contain living bacterial factories that could make an antimicrobial or other therapy – all in a programmable autonomous system. </p>
<p>This current research ties into <a href="http://doi.org/10.1002/adhm.201600908">previous work done here at the University of Maryland</a> where researchers had discovered ways to “record” biological information, by <a href="http://doi.org/10.1039/C3AN01632C">sensing the biological environment</a>, and based on the prevailing conditions, <a href="http://doi.org/10.1088/1758-5082/2/2/022002">“write” electrons to devices</a>. We and our colleagues “sent out” redox molecules from electrodes, let those molecules interact with the microenvironment near the electrode and then drew them back to the electrode so they could inform the device on what they’d seen. This mode of “molecular communication” is somewhat analogous to sonar, where redox molecules are used instead of sound waves. </p>
<p>These molecular communication efforts were used to <a href="http://doi.org/10.1021/ac302703y">identify pathogens</a>, <a href="http://doi.org/10.1021/acs.analchem.6b03620">monitor the “stress” in blood levels</a> of individuals with schizophrenia and even determine the <a href="http://doi.org/10.1038/srep18447">differences in melanin</a> from people with red hair. For nearly a decade, the Maryland team has developed methodologies to exploit redox molecules to interrogate biology by directly writing the information to devices with electrochemistry. </p>
<p>Perhaps it is now time to integrate these technologies: Use molecular communication to sense biological function and transfer the information to a device. Then use the device – maybe a small capsule or perhaps even a cellphone – to program bacteria to make chemicals and other compounds that issue new directions to the biological system. It may sound fantastical, many years away from practical uses, but our team is working hard on such valuable applications…stay tuned!</p><img src="https://counter.theconversation.com/content/71306/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Bentley receives funding from the National Science Foundation, the US Department of Agriculture, and the Department of Defense (the Defense Threat Reduction Agency, DTRA). </span></em></p><p class="fine-print"><em><span>Gregory Payne receives funding from U.S. National Science Foundation, National Institutes of Health and Department of Defense.</span></em></p>New research works out how to translate between the language of biology – molecules – and the language of microelectronics – electrons. It could open the door to new kinds of biosensors and therapeutics.William Bentley, Director, Robert E. Fischell Institute for Biomedical Devices, University of MarylandGregory Payne, Professor of Bioengineering, University of MarylandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/605972016-10-21T01:45:50Z2016-10-21T01:45:50ZThe next frontier in medical sensing: Threads coated in nanomaterials<figure><img src="https://images.theconversation.com/files/142056/original/image-20161017-12463-1t71g90.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A hydro-responsive thread can be used with sensors to monitor body functions.</span> <span class="attribution"><span class="source">Alonso Nichols, Tufts University</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Doctors have various ways to assess your health. For example, they <a href="http://dx.doi.org/10.1016/j.amjmed.2015.11.039">measure your heart rate and blood pressure</a> to indirectly assess your heart function, or straightforwardly <a href="http://dx.doi.org/10.1111/j.1537-2995.2012.03784.x">test a blood sample for iron content</a> to diagnose anemia. But there are plenty of situations in which that sort of monitoring just isn’t possible. </p>
<p>To test the <a href="https://www.researchgate.net/profile/Viktor_Lindgren/publication/268787806_Deep_infection_after_total_hip_replacement_a_method_for_national_incidence_surveillance/links/5488b0540cf2ef344790a330.pdf">health of muscle and bone in contact with a hip replacement</a>, for example, requires a complicated – and expensive – procedure. And if problems are found, it’s often too late to truly fix them. The same is true when dealing with deep wounds or internal incisions from surgery.</p>
<p>In <a href="http://nanolab.ece.tufts.edu/">my engineering lab at Tufts University</a>, we asked ourselves whether we could make sensors that could be seamlessly embedded in body tissue or organs – and yet could communicate to monitors outside the body in real time. The first concern, of course, would be to make sure that the materials wouldn’t cause infection or an immune response from the body. The sensors would also need to match the mechanical properties of the body part they would be embedded in: soft for organs and stretchable for muscle. And, ideally, they would be relatively inexpensive to make in large quantities.</p>
<p>Our search for materials we might use led us to a surprising candidate – threads, just like what our clothes are made of. Thread has many advantages. It is abundant, easy to make and very inexpensive. Threads can be made flexible and stretchable – and even from materials that aren’t rejected by the body. In addition, doctors are very comfortable working with threads: They routinely use sutures to stitch up open wounds. What if we could <a href="http://dx.doi.org/10.1038/micronano.2016.39">embed sensor functions into threads</a>?</p>
<h2>Finding the right sensor</h2>
<p>Today’s medical sensors are typically rigid and flat – which limits them to monitoring surfaces such as the scalp or skin. But most organs and tissues are three-dimensional heterogeneous multilayered biological structures. To monitor them, we need something much more like a thread.</p>
<p>Nanomaterials can be organic or inorganic, inert or bioactive, and can be designed with physical and chemical properties that are useful for medical sensing. For example, carbon nanotubes are amazingly versatile – their <a href="http://dx.doi.org/10.1002/adfm.201302344">electrical conductivity can be customized</a>, which has led to them being the basis of the next generation of sensors and electronic transistors. They can even <a href="http://dx.doi.org/10.1021/ja4000917">detect single molecules</a> of DNA and proteins. The <a href="http://dx.doi.org/10.1039/C2EE24203F">organic nanomaterial polyaniline</a> has a similarly broad range of applications, notably its conductivity depends on the strength of the acid or base it is in contact with.</p>
<h2>Making the materials</h2>
<p>To make sensing threads, we start with cotton and other conventional threads, dip them in liquids containing different nanomaterials, and rapidly dry them. Depending on the properties of the nanomaterial we use, these can monitor mechanical or chemical activity. </p>
<p>For example, coating stretchable rubber fiber with carbon nanotubes and silicone can make threads that can sense and measure physical strain. As they stretch, the threads’ electrical properties change in ways we can monitor externally. This can be used to monitor wound healing or muscle strain experienced due to artificial implants. After an implant, abnormal strain could be a sign of slow healing, or even improper placement of the device. Threads monitoring strain levels can send a message to both patient and doctor so that treatment can be modified appropriately.</p>
<p>Monitoring the electricity flow between one cotton thread coated with carbon nanotubes and polyaniline nanofibers, and another coated with silver and silver chloride, allows us to measure acidity, which can be a sign of infection.</p>
<p>To help people who need to monitor their blood sugar levels, we can coat a thread with <a href="http://dx.doi.org/10.1016/j.bios.2012.06.045">glucose oxidase</a>, which reacts with glucose to generate an electrical signal indicating how much sugar is in the patient’s blood. Similarly, coating conductive threads with other nanomaterials sensitive to specific elements or chemicals can help doctors measure potassium and sodium levels or other metabolic markers in your blood.</p>
<h2>Multiple uses</h2>
<p>Beyond sensing abilities, many thread materials, such as cotton, have another useful property: wicking. They can move liquid along their length via capillary action without needing a pump, the way <a href="http://dx.doi.org/10.1007/BF02896314">melted wax flows up a candlewick</a> to feed the flame.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=233&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=233&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=233&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=293&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=293&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142057/original/image-20161017-12443-1ru1h1i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=293&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Liquid flowing in threads sutured into skin.</span>
<span class="attribution"><span class="source">Nano Lab, Tufts University</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>We used cotton threads to transport <a href="http://dx.doi.org/10.1152/physrev.00037.2011">interstitial fluid</a>, which fills in the gaps between cells, from the places it normally exists toward sensing threads located elsewhere. The sensing threads send their electronic signals to an external device housed in a flexible patch, along with a button battery and a small antenna. There, the signals are amplified, digitized and transmitted wirelessly to a smartphone or any Wi-Fi connected device.</p>
<p>These transport-sensing measuring-transmission systems are so small that they can be powered with a tiny battery sitting on top of the skin or could <a href="http://dx.doi.org/10.1016/j.cej.2014.11.011">get energy from glucose</a> in the patient’s blood. That could allow doctors to keep a continuous eye on patients’ health remotely and unobtrusively. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=520&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=520&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=520&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=653&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=653&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142036/original/image-20161017-12447-1sm1nam.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=653&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Smart threads can monitor wounds using a suite of physical and chemical sensors made using threads and passing information to a skin-surface transmitter.</span>
<span class="attribution"><a class="source" href="https://now.tufts.edu/news-releases/researchers-invent-smart-thread-collects-diagnostic-data-when-sutured-tissue">Nano Lab, Tufts University</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>This type of integrated, wireless monitoring has several advantages over current systems. First, the patient can move around freely, rather than being confined to a hospital bed. In addition, real-time data-gathering provides much more accurate information than periodic testing at a hospital or doctor’s office. And it reduces the cost of health care by moving treatment, monitoring and diagnosis out of the hospital.</p>
<p>So far our testing of nano-infused threads has been in sterile lab environments in rodents. The next step is to perform more tests in animals, particularly to monitor how well the threads do in living tissue over long periods of time. Then we’d move toward testing in humans. </p>
<p>Now that we’ve begun exploring the possibilities of threads, potential uses seem to be everywhere. Diabetic patients can have trouble with <a href="http://dx.doi.org/10.1242/dmm.012237">wounds resisting healing</a>, which can lead to infection, and even amputation. A few choice stitches using sensing threads could let doctors detect these problems at extremely early stages – much sooner than we can today – and take action to prevent them from worsening. Sensing threads can even be woven into bandages, wound dressings or hospital bed sheets to monitor patients’ progress, and raise alarms before problems get out of control.</p><img src="https://counter.theconversation.com/content/60597/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sameer Sonkusale currently receives funding from National Science Foundation and Department of Defense.</span></em></p>Flexible, easy to make, inexpensive, stretchable and simple to coat with nanomaterials, threads are also very commonly used by doctors already.Sameer Sonkusale, Professor of Electrical and Computer Engineering, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/590392016-05-16T01:06:35Z2016-05-16T01:06:35ZA ‘sixth sense’ for humidity helps insects stay out of climatic trouble<figure><img src="https://images.theconversation.com/files/122580/original/image-20160515-10679-1deq627.jpg?ixlib=rb-1.1.0&rect=65%2C35%2C954%2C642&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Humidity levels can mean life or death for insects.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/asnalhermite/7296111892">Hasna Lahmini</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>The amount of water vapor in the air – humidity – profoundly alters our experience of the environment around us. A hot, dry morning in the desert of California feels miles apart from a hot, sticky one in the Cambodian jungle.</p>
<p>People generally dislike hot and humid conditions for good reasons. Our bodies dissipate heat through evaporation of sweat from the skin surface. When humidity is high, this process is less effective, and more blood needs to be pumped to the skin for cooling. This results in fatigue and can ultimately lead to <a href="http://www.cdc.gov/niosh/topics/heatstress/heatrelillness.html">hyperthermia (“heat stroke”)</a>.</p>
<p>Varying levels of humidity characterize all habitats on our planet. Animal species have evolved to tolerate and even to thrive in the most extreme climates, from the frozen tundras of the north to the arid deserts of the equator. It’s particularly impressive that small, cold-blooded animals such as insects can flourish in cold climates as well as in desert habitats. In part, these adaptations are made possible by sophisticated sensory systems that allow them to quickly react to potentially dangerous extremes.</p>
<p>When it comes to air humidity, scientists have known <a href="http://www.jstor.org/stable/1535970?seq=1#page_scan_tab_contents">since the early 1900s</a> that insects possess dedicated sensory systems that detect changes in water vapor in the air. This “sixth sense” for humidity has no direct parallels in big land mammals such as us. But it serves the small critters well as they work to avoid desiccation and to find open water: for example, a pond in which to lay eggs (crucial for many species of mosquitoes). We decided to investigate how these humidity-sensing systems work in insects.</p>
<h2>What’s the neuroscience underlying the system?</h2>
<p>Using our favorite fruit fly <em>Drosophila melanogaster</em> as an experimental subject, we set out to determine just how insects can detect water vapor in the air. Which neurons serve as the humidity sensors in this species? Which genes and receptor mechanisms could be used to detect changes in air humidity? How is the information about external humidity relayed and ultimately processed in the fly’s brain?</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=985&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=985&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=985&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1238&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1238&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122002/original/image-20160510-29544-1l2445u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1238&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fly species from different habitats prefer different ranges of humidity. <em>Drosophila melanogaster</em> depicted in Lund, Sweden; <em>D. mojavensis</em> depicted in the Saguaro desert of Arizona; <em>D. teissieri</em> depicted in the afrotropical rain forest.</span>
<span class="attribution"><span class="source">Gallio and Stensmyr</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>First, we had to determine the favorite humidity range for our fruit fly. Flies are human commensals – literally “share food at the same table,” in this case invited or not. But though they like to live with us, it turns out fruit flies prefer humidity that is just a touch higher than we do [~70 percent relative humidity (RH) – which, on a hot day, would feel pretty sweaty to us].</p>
<p>We also tested two related fly species that live in different habitats. <em>Drosophila mojavensis</em> lives in the arid deserts of southern California and Mexico, and in our lab tests showed a preference for drier environs. <em>Drosophila teissieri</em> lives in the rainforest, and preferred higher humidity than the two other species. This is an important result: it suggests that humidity preference is finely tuned, reflecting specific adaptations to each species’ habitat.</p>
<p>Next, we used the powerful tools available to fruit fly geneticists to find genes that are essential for this ability to detect and respond to air humidity. In flies, we can turn genes on or off relatively easily via mutation, as well as artificially activating or silencing specific neurons to observe what happens to behavior as a result.</p>
<p>The logic here was simple: if we find genes that, when missing, make the flies insensitive to changes in humidity, we know those genes are normally involved in that sensory system. Once we identify those genes, we can determine where they’re active so we can pinpoint which neurons serve as humidity detectors.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=530&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=530&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=530&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=667&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=667&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122004/original/image-20160510-20734-1ts99pe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=667&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The fruit fly <em>Drosophila</em> detects air humidity through hygroreceptors (green) located in a small sac-like invagination of the antenna.</span>
<span class="attribution"><span class="source">Gallio and Stensmyr</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Long story short, we <a href="http://dx.doi.org/10.1016/j.cub.2016.03.049">identified three related genes</a> without which flies become “blind” to external humidity. Flies missing them show no preference at all for dry or humid air. It turned out that they function within key receptor neurons located in the antenna. They’re found in an unusual little pouch in the back of the antenna called the “sacculus” (literally ‘little sac’) – well-protected from potential water splashes or other dangers. </p>
<p>These humidity detectors – termed “hygroreceptors” from the Greek word for humidity – rapidly respond to a puff of dry air, potentially alerting the animal to the fact that dangerous dry conditions are looming. </p>
<p>Next, we followed the projections of the hygroreceptor neurons into the brain, and discovered they end in a region right next to the one that we’ve previously shown is <a href="http://dx.doi.org/10.1016/j.cell.2011.01.028">targeted by temperature receptors of the antenna</a>. Indeed, in insects, temperature and humidity appear to be detected by distinct receptor systems. But the two will of course interact in the brain to determine how attractive a climate may ultimately be to the fly.</p>
<h2>How evolution and engineers approach humidity</h2>
<p>Discoveries like these reveal some of the clever ways evolution solved basic engineering problems. These solutions are invariably a source of inspiration to human engineers working on related areas. In fact, it is quite interesting to compare how flies measure humidity with how we do it.</p>
<p>Modern hygrometers often rely on changes in the electrical properties of a hygroscopic – “moisture-absorbing” – material. Before the reign of electronics, a number of clever strategies had been used to achieve this same goal. Some of the earliest hygrometers were likely inspired by the common “bad hair day” experience: human and animal hair are strongly hygroscopic and change in shape and length depending on air humidity.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=955&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=955&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=955&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1200&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1200&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122581/original/image-20160515-12583-1s2321y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1200&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The hair hygrometer, invented by de Saussure in 1783.</span>
</figcaption>
</figure>
<p>Leonardo da Vinci built the <a href="http://www.museoscienza.org/english/leonardo/models/macchina-leo.asp?id_macchina=43">first-ever hygrometer</a> on this principle in 1480. A more sophisticated instrument (that can be <a href="http://www.scientificamerican.com/article/bring-science-home-hair-hygrometer/">easily built as part of a science class</a>) is the famous “hair-hygrometer” invented by the Swiss physicist Horace Bénédict de Saussure in 1783. Here, a single human hair is extended over a pulley that operates a needle, so that changes in the hair’s length can be easily measured to keep track of changes in external humidity.</p>
<p>As it turns out, the fly may use a very similar strategy to measure humidity: the tips of the hygrosensory neurons we discovered are located within tiny hairs (sensilla) in the sacculus. We believe mechanical deformation of these sensilla may ultimately help the fly keep track of humidity levels.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122583/original/image-20160515-10658-cqekqj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Freshly hatched <em>Culex</em> mosquito, with swimming larvae in the background.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/canoarias/14875299141">Cano Vääri</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<h2>Applying hygrometer knowledge in the field</h2>
<p>Understanding how animals sense and respond to key environmental parameters helps us understand how they adapt to their surroundings, and will help us predict what will happen to the distribution and survival of species as the climate changes as a result of global warming.</p>
<p>Moreover, an increasing knowledge of the cogs and gears that pesky insects like mosquitoes use to navigate their environment and find their “prey” suggests new ways to steer them away from us. For instance, researchers are working on <a href="http://www.theatlantic.com/science/archive/2016/01/the-troubled-quest-to-find-a-better-mosquito-repellent/423672/">scrambling the olfactory system of mosquitoes</a>, which they use to locate their blood meals. Our new findings may lead to additional strategies for controlling insect populations, perhaps by leading them away from bodies of water near our cities.</p>
<p><em>We would like to thank the people in our laboratories who conducted most of the work described here: Anders Enjin (catalyst of the collaboration between our two Labs), Emanuela E. Zaharieva, Dominic D. Frank, Suzan Mansourian, as well as our colleague Greg S.B. Suh (NYU) for his contribution.</em></p><img src="https://counter.theconversation.com/content/59039/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marco Gallio receives funding from NIH and Northwestern University. Previous sources of funding include: HHMI, HFSP, The Wenner-Grens Institute</span></em></p><p class="fine-print"><em><span>Marcus Stensmyr receives funding from The Swedish Research Council and The Crafoord Foundation. </span></em></p>Detecting drier or wetter conditions is crucial for insect survival. We’ve long known they can do this – now researchers have discovered the genetic and neural basis for their humidity-sensing system.Marco Gallio, Assistant Professor of Neurobiology, Northwestern UniversityMarcus Stensmyr, Senior Lecturer of Biology, Lund UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/450322015-08-07T10:03:40Z2015-08-07T10:03:40ZTaking plants off planet – how do they grow in zero gravity?<figure><img src="https://images.theconversation.com/files/91081/original/image-20150806-5209-8ine5y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Astronaut Cady Coleman harvests one of our plants on Space Shuttle Columbia.</span> <span class="attribution"><span class="source">NASA</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Gravity is a constant for all organisms on Earth. It acts on every aspect of our physiology, behavior and development – no matter what you are, you evolved in an environment where gravity roots us firmly to the ground.</p>
<p>But what happens if you’re removed from that familiar environment and placed into a situation outside your evolutionary experience? That’s exactly the question we ask every day of the plants we grow <a href="http://ufspaceplants.org/">in our laboratory</a>. They start out here in our earthbound lab, but they’re on their way to outer space. What could be a more novel environment for a plant than the zero-gravity conditions of spaceflight?</p>
<p>By studying how plants react to life in space, we can learn more about how they adapt to environmental changes. Not only are plants crucial to almost every facet of life on Earth; plants will be critical to our explorations of the universe. As we look to a future of possible space colonization, it’s vital to understand how plants will fare off planet before we rely on them within space outposts to recycle our air and water and supplement our food.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=515&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=515&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91057/original/image-20150806-5245-f4vboc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=515&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Astronaut Jeff Williams harvests our Arabidopsis plants on the ISS.</span>
<span class="attribution"><span class="source">NASA</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>So even while we stay right here on the ground, <a href="http://www.nasa.gov/mission_pages/station/research/experiments/709.html">our research plants</a> blast off and head to the <a href="http://www.nasa.gov/mission_pages/station/main/index.html">International Space Station</a> (ISS). Already they’ve given us some surprises about growing in zero gravity – and shaken up some of our thinking about how plants grow on Earth.</p>
<h2>Learning from stressed-out plants</h2>
<p>Plants make especially great research subjects if you’re interested in environmental stress. Because they’re stuck in one spot – what we biologists call sessile organisms – plants must cleverly deal in place with whatever their environment throws at them. Moving to a more favorable spot isn’t an option, and they can do little to alter the environment around them.</p>
<p>But what they can do is alter their internal “environment” – and plants are masters of manipulating their metabolism to cope with perturbations of their surroundings. This characteristic is one of the reasons we use plants in our research; we can count on them to be sensitive reporters of environmental change, even in novel environments like spaceflight.</p>
<p>Folks have been curious about how plants respond to spaceflight from the very beginning of our ability to get there. We launched <a href="http://www.ncbi.nlm.nih.gov/pubmed/11402191">our first spaceflight experiment</a> on Space Shuttle Columbia back in 1999, and the things we learned then are still fueling new hypotheses about how plants deal with the absence of gravity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91054/original/image-20150806-5209-19h6t3u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Authors Robert Ferl (front) and Anna-Lisa Paul (middle) conduct a plant experiment in the microgravity conditions of NASA’s parabolic flight aircraft.</span>
<span class="attribution"><span class="source">NASA</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>We’re in Florida, our research plants are in space</h2>
<p>Spaceflight requires specialized growth habitats, specialized tools for observation and sample collection, and of course specialized people to take care of the experiment on orbit.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=703&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=703&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=703&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=883&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=883&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91052/original/image-20150806-5233-u2l6eq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=883&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The Advanced Biological Research System spaceflight hardware showing the Petri plates with plants.</span>
<span class="attribution"><span class="source">Anna-Lisa Paul</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>A typical experiment begins on Earth in our lab with the planting of dormant Arabidopsis seeds in Petri plates containing a nutrient gel. This gel (unlike soil) stays put in zero gravity, and provides the water and nutrients the growing plants will need. The plates are then wrapped in dark cloth, taken to Kennedy Space Center, and eventually loaded into the Dragon Capsule on top of a Falcon 9 rocket to catch a ride to the ISS.</p>
<p>Once docked, an astronaut inserts the plates into the plant growth hardware. The light inside stimulates the seeds to sprout, cameras record the growth of the seedlings over time, and at the end of the experiment, the astronaut harvests the 12-day-old plants and save them in tubes of preservative.</p>
<p>Once returned to us on Earth, we can run more tests on the preserved samples to investigate the unique metabolic processes the plants engaged while on orbit.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91056/original/image-20150806-5233-1nalc12.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The imaging system we built with colleagues to capture fluorescent plant gene expression data during parabolic flight and, eventually, suborbital operations.</span>
<span class="attribution"><span class="source">Robert Ferl</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Unraveling it back in the lab</h2>
<p>One of the first things we found was that certain root growth strategies that everyone had assumed need gravity actually don’t require it at all.</p>
<p>To seek out water and nutrients, plants need their roots to grow away from where they are planted. On Earth, gravity is the most important “cue” for the direction to grow, but plants also use touch (think of the root tip as a sensitive fingertip) to help navigate around obstacles.</p>
<p>Back in 1880, Charles Darwin showed that when you grow plants along a slanted surface, the roots don’t grow straight away from the seed, but rather take a jog to one side. This root growth strategy is called “skewing.” <a href="http://www.freeinfosociety.com/media/pdf/4790.pdf">Darwin hypothesized</a> that a combination of gravity and the root touching its way across the surface was behind it - and for 130 years, that’s what everyone else thought too.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/fF0eHg4aX_Y?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Roots grew with skew – without gravity.</span></figcaption>
</figure>
<p>But in 2010, we saw that the roots of the plants we grew on the ISS marched across the surface of their Petri plate in a <a href="http://dx.doi.org/10.1186/1471-2229-12-232">perfect example of root skewing</a> – no gravity required. It was quite a surprise. So what’s really behind root-skewing on orbit, since it’s obviously not gravity?</p>
<p>Plants on the ISS do have a potentially second source of information from which they could get a directional cue: light. We hypothesized that in the absence of gravity to point roots “away” from the direction of the leaves, light plays a bigger role in root guidance.</p>
<p>What we found was that yes, light is important, but not just any light will do – there has to be a gradient of light intensity for it to act as a useful guide. Think of it in terms of a good smell: you can navigate to the kitchen with your eyes closed when cookies are just coming out of the oven, but if the whole house is flooded equally with the scent of chocolate chip cookies, you couldn’t find your way.</p>
<h2>Adjusting their metabolic toolbox on the fly</h2>
<p>In the absence of gravity, plants can’t use the “tools” they’re used to for navigation, so they had to craft together another solution. They can do that by regulating the way they express their genes. That way they can make more or less of specific proteins that are helpful or not in zero gravity. Various plant parts came up with their own gene regulation strategies.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/IvmPc4j25ao?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Glowing plants let us see which genes are active, so we can tell which proteins are being made.</span></figcaption>
</figure>
<p>We found a number of genes involved in making and remodeling cell walls are <a href="http://dx.doi.org/10.1186/1471-2229-13-112">expressed differently</a> in space-grown plants. Other genes involved with light-sensing – normally expressed in leaves on Earth – are expressed in roots on the ISS. In leaves, many genes associated with plant hormone signaling are repressed, and genes associated with insect defense are more active. <a href="http://dx.doi.org/10.1089/ast.2014.1210">These same trends</a> are also seen in the relative abundance of proteins involved in signaling, cell wall metabolism and defense.</p>
<p>These patterns of genes and proteins tell a story – in microgravity, plants respond by loosening their cell walls, along with creating new ways to sense their environment.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91055/original/image-20150806-5260-1vctak6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Engineered Arabidopsis plants. Green color shows where green fluorescent protein (GFP) is being expressed, and red shows the natural fluorescence of chlorophyll.</span>
<span class="attribution"><span class="source">Anna-Lisa Paul</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We track these gene expression changes in real time by labeling specific proteins with a fluorescent tag. Plants engineered with <a href="https://theconversation.com/fluorescent-proteins-light-up-science-by-making-the-invisible-visible-39272">glowing fluorescent proteins</a> can then “report” how they are responding to their environment as it is happening. These engineered plants act as biological sensors – “biosensors” for short. Specialized cameras and microscopes let us follow how the plant is utilizing those fluorescent proteins.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/purGp-1juCE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The authors inside the “Vomit Comet” that recreates microgravity conditions on Earth.</span></figcaption>
</figure>
<h2>Insights from space</h2>
<p>This kind of research gives us new understanding of how plants sense and respond to external stimuli at a fundamental, molecular level. The more we can learn about how plants respond to novel and extreme environments, the more prepared we are for understanding how plants will deal with the changing environments they’re up against here on Earth.</p>
<p>And of course our research will inform collective efforts to take our biology off the planet. The observation that gravity isn’t as vital to plants as we once thought is welcome news for the prospect of farming on other planets with low gravity, and even on spacecraft where there is no gravity. Humans are explorers, and when we leave earth’s orbit, you can bet we’ll take plants with us!</p><img src="https://counter.theconversation.com/content/45032/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anna-Lisa Paul receives funding from NASA research grants.</span></em></p><p class="fine-print"><em><span>Robert Ferl receives funding from NASA.</span></em></p>Plants on the International Space Station must figure out how to grow in a completely novel environment. Their adaptability hints at how they’ll react to changes here on Earth – or in future space outposts.Anna-Lisa Paul, Research Professor, Graduate Faculty in Plant Molecular and Cellular Biology, University of FloridaRobert Ferl, Director of the Interdisciplinary Center for Biotechnology Research, University of FloridaLicensed as Creative Commons – attribution, no derivatives.