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Swallow a Tiny Capsule to Check Your Gut! by ROSS TESTER Researchers at two Melbourne universities have come up with a new way to analyse the gases in your gut, which could provide answers to many medical mysteries. And that information can be transmitted instantly to a smartphone app via Bluetooth. W e’re all used to swallowing capsules containing medicine. They’re designed to stay “sealed” until they reach a part of the body where the medicine needs to go, then the capsule dissolves. For example, depending on the capsule skin composition and/or thickness, it might stay intact until it reaches the stomach, or the intestine, etc. More recently, medical specialists have been using another type of “capsule”, one definitely not designed to break down because it contains an ultra-miniature camera, along with a light source and a memory card. They’re intended to take photos every so often as they pass right through the system. After a period of up to few days, they’re recovered (use your own imag- ination!) and the photos are analysed (perhaps a poor choice of word, there) to find evidence of, say, ulcers, blockages, cancers and other nasties. After suitable treatment, the camera can be used over and over – they’re still too expensive to be throw-away items, though that is changing. Another type of capsule can be used to measure and analyse body temperature, respiration, blood and waste chemistry and so on. But until now, they’ve all suffered the same disadvantage – clinicians had to wait until the capsule emerged before the data could be read. Gas-sniffing capsule A group of researchers from Melbourne, led by Kourosh KalantarZadeh of RMIT University and Peter Gibson of Monash University has recently published a paper in “Nature Electronics” detailing a tiny ingestible electronic capsule which reports, via radio, the concentration of various gases in the human gut. When paired with a pocket-sized receiver and a mobile phone app, the pill reports conditions in real-time as it passes from the stomach to the colon. Such data could clarify the conditions of each section of the gut, what microbes are up to and which foods may cause problems in the system. Until now, collecting such data has been a challenge. Methods to bottle it involved cumbersome and invasive tubing and inconvenient whole-body calorimetry. Early human trials of the gas-smiffing capsule have already hinted that The electronics are packed into a capsule measuring just 26 x 9.8mm. It uses a receiver connected to a smartphone app. 24 Silicon Chip Celebrating 30 Years siliconchip.com.au At 26 x 9.8mm, it’s larger than typical medicine capsules – but still well within the “comfort zone” of most people. the pill can provide new information about intestinal wind patterns and gaseous turbulence from different foods. The capsule is made according to the “000” standard: 26mm in length, with a 9.8mm external diameter. It includes sensors for CO2, H2 and O2 gases that occur in various aerobic and anaerobic conditions, a temperature sensor, a microcontroller and a 433MHz transmission system plus the button cells which power it. One end of the capsule contains a gas-permeable membrane that allows for fast diffusion of gut gases. A non-transparent, polyethylene shell houses the internal electronic components. The polymer shell is machined in two pieces, sealed together using a bio-compatible adhesive. Interestingly, the capsule was made non-transparent, as volunteers showed hesitation in swallowing capsules with transparent covers, where they could see the electronic circuits inside. A combination of thermal conductivity and semiconducting sensors, with an extraction algorithm, generate the gas profiles and determine the gas concentration in both aerobic and anaerobic segments of the gut. siliconchip.com.au The gas-sensing capsule uses a separate receiver which can be linked by Bluetooth to a smartphone or computer. It is not yet in commercial production. Celebrating 30 Years May 2018  25 Inside the gut gas measuring capsule prototype. It is made from non-transparent material because volunteers showed a reluctance to swallow anything where they could see electronics inside! Capsule accuracy for measuring H2 and O2 was found to be better than 0.2%, and for CO2 it was 1%. The key technological differences between human gas sensing capsules and those used for animal trials on pigs is the implementation of an advanced gas detection algorithm. This uses heat modulation to distinguish between H2 and CO2 with much higher accuracy. An oxygen sensor is included to locate the capsule in different gut segments, along with a temperature sensor to measure the core body temperature and sense the excretion of the capsule out of the body of volunteers (when the temperature drops below 35°C). The capsules also incorporate membranes with embedded nanomaterials that allow for the fast diffusion of dissolved gases, while efficiently blocking liquid. Following trials on pigs, the researchers tested the capsule in six healthy people. For the first, researchers monitored the pill’s intestinal trek using ultrasound and linked locations with gas profiles. Overall, it took 20 hours to get from one end to the other, spending 4.5 hours in the stomach, 2.5 hours in the small intestine, and 13 hours cruising through the colon. In that time, the pill took continuous gas measurements, revealing potentially useful information in addition to gut position. For instance, CO2 and H2 levels peaked in the early hours of its time in the colon while O2 levels crashed throughout this stretch of the trip. That correlates with how anaerobic bacteria (those that live without oxygen) inhabit the colon and ferment undigested food into short-chain fatty acids that play significant roles in our health and metabolism. In the next human trial, the researchers had one person swallow the pill twice. The first time, he ate a very highfibre diet (50 grams per day) for two days prior to swallowing the pill. Two weeks later, he swallowed another pill after eating a low-fibre diet (15 grams per day) for two days. In the high-fibre test, the man passed the pill in about 23 26 Silicon Chip One end of the capsule has a semi-permeable membrane to allow gases to enter and be analysed; however liquids are prevented from entering hours. But he was not happy about it. The super dose of fibre caused abdominal pain. In its four hours in the colon, the pill recorded elevated levels of O2, which could mess up anaerobes. Indeed, an analysis of fecal bacteria during this phase showed a shift toward species associated with poor gut health. There were also problems in the low-fibre scenario. The pill took a little more than three days to work its way out. It spent 13 hours in the stomach, 5.5 hours in the small intestines, and a huge 54 hours in the colon. In fact, about 36 hours after taking the pill, the man was given a high dose of fibre to try to move things along. Prior to that fibre intervention, H2 gas levels in the colon had plummeted, suggesting a drop off in fermentation. It picked back up 12 hours after the fibre treatment. Last, the researchers recruited four more healthy patients to pass the pill. Two ate a high-fibre diet (though not quite as high as the first trial), while the remaining two ate a low fibre diet. This showed similar patterns seen in the earlier trials. In an accompanying editorial, mechanical engineer Benjamin Terry of the University of Nebraska-Lincoln concluded that the capsules “have remarkable potential to help us understand the functional aspects of the gut microbiome, its response to dietary changes, and its impact on health.” “It might not be too long before a routine healthcare visit involves a check of your vital signs and a request to swallow a tiny electronic monitoring device,” he added. SC Acknowledgement: Information based on Nature Electronics, Vol 1, January 2018 Celebrating 30 Years siliconchip.com.au