An inexpensive portable biosensor developed by researchers at Brazil’s National Nanotechnology Laboratory (credit: LNNano)
A novel nanoscale organic transistor-based biosensor that can detect molecules associated with neurodegenerative diseases and some types of cancer has been developed by researchers at the National Nanotechnology Laboratory (LNNano) in Brazil.
The transistor, mounted on a glass slide, contains the reduced form of the peptide glutathione (GSH), which reacts in a specific way when it comes into contact with the enzyme glutathione S-transferase (GST), linked to Parkinson’s, Alzheimer’s and breast cancer, among other diseases.
Sensitive water-gated copper phthalocyanine (CuPc) thin-film transistor (credit: Rafael Furlan de Oliveira et al./Organic Electronics)
“The device can detect such molecules even when they’re present at very low levels in the examined material, thanks to its nanometric sensitivity,” explained Carlos Cesar Bof Bufon, Head of LNNano’s Functional Devices & Systems Lab (DSF).
Bufon said the system can be adapted to detect other substances by replacing the analytes (detection compounds). The team is working on paper-based biosensors to further lower the cost, improve portability, and facilitate fabrication and disposal.
The research is published in the journal Organic Electronics.
Abstract of Water-gated phthalocyanine transistors: Operation and transduction of the peptide–enzyme interaction
The use of aqueous solutions as the gate medium is an attractive strategy to obtain high charge carrier density (1012 cm−2) and low operational voltages (<1 V) in organic transistors. Additionally, it provides a simple and favorable architecture to couple both ionic and electronic domains in a single device, which is crucial for the development of novel technologies in bioelectronics. Here, we demonstrate the operation of transistors containing copper phthalocyanine (CuPc) thin-films gated with water and discuss the charge dynamics at the CuPc/water interface. Without the need for complex multilayer patterning, or the use of surface treatments, water-gated CuPc transistors exhibited low threshold (100 ± 20 mV) and working voltages (<1 V) compared to conventional CuPc transistors, along with similar charge carrier mobilities (1.2 ± 0.2) x 10−3 cm2 V−1 s−1. Several device characteristics such as moderate switching speeds and hysteresis, associated with high capacitances at low frequencies upon bias application (3.4–12 μF cm−2), indicate the occurrence of interfacial ion doping. Finally, water-gated CuPc OTFTs were employed in the transduction of the biospecific interaction between tripeptide reduced glutathione (GSH) and glutathione S-transferase (GST) enzyme, taking advantage of the device sensitivity and multiparametricity.
An atherosclerotic lesion. Such lesions can rupture and cause heart attacks and strokes. (credit: UVA School of Medicine)
University of Virginia School of Medicine have discovered that a gene called Oct4 — which scientific dogma insists is inactive in adults — actually plays a vital role in preventing ruptured atherosclerotic plaques inside blood vessels, the underlying cause of most heart attacks and strokes.
The researchers found that Oct4 controls the conversion of smooth muscle cells into protective fibrous “caps” inside plaques, making the plaques less likely to rupture. They also discovered that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques. In addition, the researchers believe it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a way to reduce the incidence of heart attacks or stroke.
Could impact many human diseases, regenerative medicine
The researchers are also currently testing Oct4′s possible role in repairing cellular damage and healing wounds, which would make it useful for regenerative medicine.
Oct4 is one of the “stem cell pluripotency factors” described by Shinya Yamanaka, PhD, of Kyoto University, for which he received the 2012 Nobel Prize. His lab and many others have shown that artificial over-expression of Oct4 within somatic cells grown in a lab dish is essential for reprogramming these cells into induced pluripotential stem cells, which can then develop into any cell type in the body or even an entire organism.
“Finding a way to reactivate this pathway may have profound implications for health and aging,” said researcher Gary K. Owens, director of UVA’s Robert M. Berne Cardiovascular Research Center. “This could impact many human diseases and the field of regenerative medicine. [It may also] end up being the ‘fountain-of-youth gene,’ a way to revitalize old and worn-out cells.”
The discovery is described in a paper published online in Nature Medicine. The work was funded by the National Institutes of Health, the Russian Science Foundation, the Russian Federal Agency of Scientific Organization, and the U.S. Department of Defense.
Abstract of Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective
Although somatic cell activation of the embryonic stem cell (ESC) pluripotency factor OCT4 has been reported, this previous work has been controversial and has not demonstrated a functional role for OCT4 in somatic cells. Here we demonstrate that smooth muscle cell (SMC)-specific conditional knockout of Oct4 in Apoe−/− mice resulted in increased lesion size and changes in lesion composition that are consistent with decreased plaque stability, including a thinner fibrous cap, increased necrotic core area, and increased intraplaque hemorrhage. Results of SMC-lineage-tracing studies showed that these effects were probably the result of marked reductions in SMC numbers within lesions and SMC investment within the fibrous cap, which may result from impaired SMC migration. The reactivation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4promoter and was hypoxia inducible factor-1α (HIF-1α, encoded by HIF1A) and Krüppel-like factor-4 (KLF4)-dependent. These results provide the first direct evidence that OCT4 has a functional role in somatic cells, and they highlight the potential role of OCT4 in normal and diseased somatic cells.
Stanford University School of Engineering | This easy-to-assemble black box is part of an experimental urinalysis testing system designed by Stanford engineers. The black box is meant to enable a smartphone camera to capture video that accurately analyzes color changes in a standard paper dipstick to detect conditions of medical interest.
Two Stanford University electrical engineers have designed a simple new low-cost, portable urinalysis device that could allow patients to get consistently accurate urine test results at home.
The system uses a black box and smartphone camera to analyze a standard color-changing paper test, using a medical dipstick dipped into the urine specimen, to measure levels of glucose, blood, protein, and other chemicals — which can indicate evidence of kidney disease, diabetes, urinary tract infections and even signs of bladder cancer.
The current standard dipstick test uses a paper strip with 10 square pads. Dipped in a sample, each pad changes color to screen for the presence of a different disease-indicating chemical. After waiting the appropriate amount of time, a medical professional — or, increasingly, an automated system — compares the pad shades to a color reference chart for results.
But the test takes time, costs money, and creates backlogs for clinics and primary care physicians. The results are often inconclusive, requiring both patient and doctor to book another appointment. So patients with long-term conditions like chronic urinary tract infections must wait for results to confirm what both patient and doctor already know before getting antibiotics. Tracking patients’ progress with multiple urine tests a day is out of the question.
Some innovators have tried to create simple, do-it-yourself systems, but they can be error-prone, said Audrey (Ellerbee) Bowden, assistant professor of electrical engineering at Stanford. “You think it’s easy — you just dip the stick in urine and look for the color change, but there are things that can go wrong,” she said. “Doctors don’t end up trusting those results as accurate.”
A simplified home urinanalysis system
Prototype urinalysis device (credit: Gennifer T. Smith et al./Lab on a Chip)
Writing in Lab on a Chip, a journal of the Royal Society of Chemistry, Bowden and Gennifer Smith, a PhD student in electrical engineering, explain they designed their system to overcome three main potential errors in a home test: inconsistent lighting, urine volume control, and timing.
To fix this, the engineers designed a multi-layered system to load urine onto the dipstick. A dropper squeezes urine into a hole in the first layer, filling up a channel in the second layer, and ten square holes in the third layer. Some clever engineering ensures that a uniform volume of urine is deposited on each of the ten pads on the dipstick at just the right time.
Finally, a smartphone is placed on top of the black box with the video camera focused on the dipstick inside the box. Custom software reads video from the smartphone and controls the timing and color analysis.
To perform the test a person would load the urine and then push the third layer into the box. When the third layer hits the back of the box, it signals the phone to begin the video recording at the precise moment when the urine is deposited on the pads.
Timing is critical to the analysis. Pads have readout times ranging from 30 seconds to 2 minutes. Once the two minutes are up, the person can transfer the recording to a software program on their computer. For each pad, it pulls out the frames from the correct time and reads out the results.
The engineers also plan to design an app to send the results directly to the doctor.
Funding for this research came from the National Institutes of Health, the Rose Hills Foundation Graduate Engineering Fellowship, the Electrical Engineering Department New Projects Graduate Fellowship, the Oswald G. Villard Jr. Engineering Fellowship, the Stanford Graduate Fellowship and the National Science Foundation Graduate Research Fellowship.
Abstract of Robust dipstick urinalysis using a low-cost, micro-volume slipping manifold and mobile phone platform
We introduce a novel manifold and companion software for dipstick urinalysis that eliminate many of the aspects that are traditionally plagued by user error: precise sample delivery, accurate readout timing, and controlled lighting conditions. The proposed all-acrylic slipping manifold is reusable, reliable, and low in cost. A simple timing mechanism ensures results are read out at the appropriate time. Results are obtained by capturing videos using a mobile phone and by analyzing them using custom-designed software. We show that the results obtained with the proposed device are as accurate and consistent as a properly executed dip-and-wipe method, the industry gold-standard, suggesting the potential for this strategy to enable confident urinalysis testing in home environments.
An “origami robot” unfolds itself from an ingestible capsule. It could be used by a physician to perform a remote-controlled operation (credit: Melanie Gonick/MIT)
MIT researchers and associates have developed a tiny “origami robot” that can unfold itself from a swallowed capsule and, steered by a physician via an external magnetic field, crawl across the stomach wall to operate on a patient. For example, it can remove a swallowed button battery or patch a wound.
System for remote-controlled clinical procedures via origami-based robot. A patient swallows an iced capsule, which melts when it reaches the stomach, releasing the robot from a folded origami structure. To remove a foreign body (such as a button battery), the physician controls the robot from outside the body via a magnetic field that affects the magnet inside the delivery structure, allowing the robot to push the foreign body into the GI system. The robot can also treat an inflammation by releasing a drug contained in the delivery structure. (credit: Shuhei Miyashita et al./ICRA Proceedings)
Every year, 3,500 swallowed button batteries are reported in the U.S. alone. Frequently, the batteries are digested normally, but if they come into prolonged contact with the tissue of the esophagus or stomach, they can cause an electric current that produces hydroxide, which burns the tissue.
The researchers at MIT, the University of Sheffield, and the Tokyo Institute of Technology presented the work last week at the International Conference on Robotics and Automation. The design built on previous work (see related links below) from the research group of Daniela Rus, the Andrew and Erna Viterbi Professor in MIT’s Department of Electrical Engineering and Computer Science. The new robot is a successor to one reported at this conference last year, with an improved design, tested in a pig stomach.
Rus and the team plan further developments, including the robot’s ability to perform procedures without physician remote control.
MIT | Ingestible origami robot
Abstract of Ingestible, Controllable, and Degradable Origami Robot for Patching Stomach Wounds
Developing miniature robots that can carry out versatile clinical procedures inside the body under the remote instructions of medical professionals has been a long time challenge. In this paper, we present origami-based robots that can be ingested into the stomach, locomote to a desired location, remove a foreign body, deliver drugs, and biodegrade. We designed and fabricated composite material sheets for a biocompatible and biodegradable robot that can be encapsulated in ice for delivery through the esophagus, embed a drug layer that is passively released to a wounded area, and be remotely controlled to carry out underwater maneuvers specific to the tasks using magnetic fields. The performances of the robots are demonstrated in a simulated physical environment consisting of an esophagus and stomach with properties similar to the biological organs.
New material temporarily protects and tightens skin, and smoothes wrinkles. (credit: Olivo Labs)
MIT scientists and associates have developed a new material that can temporarily protect and tighten skin, and smooth wrinkles. With further development, it could also be used to deliver drugs to help treat skin conditions such as eczema.
The material is a silicone-based polymer that could be applied on the skin as a thin, imperceptible coating, mimicking the mechanical and elastic properties of healthy, youthful skin.
In tests with human subjects, the researchers found that the material was able to reshape “eye bags” under the lower eyelids and also enhance skin hydration (moisturizing, or preventing the skin from dying out). This type of “second skin” could also be adapted to provide long-lasting ultraviolet protection, the researchers say.
Mimicking skin
As skin ages, it becomes less firm and less elastic — problems that can be exacerbated by sun exposure. This process impairs skin’s ability to protect against extreme temperatures, toxins, microorganisms, radiation, and injury. About 10 years ago, the MIT-headed research team set out to develop a protective coating that could restore the properties of healthy skin, for both medical and cosmetic applications.
An invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. (credit: Melanie Gonick/MIT)
The idea was to control the properties of skin by coating it with polymers that would impart beneficial effects, while making the coating invisible and comfortable.
“It has to have the right optical properties, otherwise it won’t look good, and it has to have the right mechanical properties, otherwise it won’t have the right strength and it won’t perform correctly,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute. Langer is the senior author of a paper describing the polymer in the May 9 online issue of Nature Materials.
The researchers created a library of more than 100 possible polymers with the chemical structure known as siloxane — a chain of alternating atoms of silicon and oxygen. These polymers can be assembled into a network arrangement known as a cross-linked polymer layer (XPL).
The researchers then tested the materials in search of one that would best mimic the appearance, strength, and elasticity of healthy skin.
Two-step topical application of Olivo film (credit: Olivo Labs)
The best-performing material they found has elastic properties very similar to those of human skin. In laboratory tests, it easily returned to its original state after being stretched more than 250 percent (natural skin can be elongated about 180 percent). In laboratory tests, the novel XPL’s elasticity was much better than that of two other types of wound dressings now used on skin — silicone gel sheets and polyurethane films.
In the paper, researchers describe studies performed on humans to test the material’s effectiveness in terms of wearability, prevention of water loss, and safety. In wearability, the XPL material outperformed two commercial wound dressings with respect to flexibility, elasticity, thickness and visibility. In moisturization (hydration) and water loss, XPL exhibited statistically less water loss and more skin-hydration than high-end commercial moisturizers. Additionally, no skin irritation was observed in these tests.
The XPL is currently delivered in a two-step process. First, polysiloxane components are applied to the skin, followed by a platinum catalyst that induces the polymer to form a strong cross-linked film that remains on the skin for up to 24 hours. This catalyst has to be added after the polymer is applied because after this step the material becomes too stiff to spread. Both layers are applied as creams or ointments, and once spread onto the skin, XPL becomes essentially invisible.*
MIT | Engineering a second skin
The new material was developed at MIT spinoff Living Proof, which has now spun out the XPL technology to Olivo Laboratories, LLC. Initially, Olivo’s team will focus on medical applications of the technology for treating skin conditions such as dermatitis.
“This ‘skin conforming’ platform brings with it transport properties that have significant promise to treat underlying conditions,” said Dr. Rox Anderson, Harvard Professor, Olivo co-founder, and Dermatologist at Massachusetts General Hospital, where researchers were also involved in the research. “For eczema or sun protection as examples, this second skin platform can then serve as a reservoir for control-release transdermal drug delivery or SPF ingredients, a possibility we are currently pursuing in our lab.”
A beauty business based on MIT bioengineering
Jennifer Aniston is co-owner of Living Proof, a hair care company whose products are based on discoveries at MIT’s Langer Lab (credit: Living Proof)
Living Proof, a hair care company with roots in research emerging from the Langer Lab at MIT, has won 80 awards and counting and retails in 33 countries plus Hong Kong.
Fronted by celebrity spokesperson and co-owner Jennifer Aniston, Living Proof has formulated hair products that capitalize on the properties of octaflouropentyl methacrylate, or OFPMA, which is both hydrophobic and lipophobic (repels both water and fat). “It lays down on the surface and changes how moisture moves in and out of the fiber,” Spengler explains. “That has a profound influence on the quality of hair.”
The researchers have also discovered poly beta-amino ester (PBAE), which deposits a flexible pattern of thickening points that create space between each hair strand, making fine hair feel fuller.
* The researchers performed several studies in humans to test the material’s safety and effectiveness. In one study, the XPL was applied to the under-eye area where “eye bags” often form as skin ages. These eye bags are caused by protrusion of the fat pad underlying the skin of the lower lid. When the material was applied, it applied a steady compressive force that tightened the skin, an effect that lasted for about 24 hours.
In another study, the XPL was applied to forearm skin to test its elasticity. When the XPL-treated skin was distended with a suction cup, it returned to its original position faster than untreated skin.
The researchers also tested the material’s ability to prevent water loss from dry skin. Two hours after application, skin treated with the novel XPL suffered much less water loss than skin treated with a high-end commercial moisturizer. Skin coated with petrolatum was as effective as XPL in tests done two hours after treatment, but after 24 hours, skin treated with XPL had retained much more water. None of the study participants reported any irritation from wearing XPL.
Abstract of An elastic second skin
We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat- or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (<40%), and that withstands elongations exceeding 250%, elastically recoiling with minimal strain-energy loss on repeated deformation. The application of XPL to the herniated lower eyelid fat pads of 12 subjects resulted in an average 2-grade decrease in herniation appearance in a 5-point severity scale. The XPL platform may offer advanced solutions to compromised skin barrier function, pharmaceutical delivery and wound dressings.
The common causes of death in the United States in 2013 (credit: BMJ)
Medical error is the third leading cause of death in the U.S. after heart disease and cancer — an estimated 210,000 to 400,000 deaths a year among hospital patients — say experts in an open-access paper in the British Medical Journal — despite the fact that both hospital reporting and death certificates in the U.S. have no provision for acknowledging medical error.
Martin Makary and Michael Daniel at Johns Hopkins University School of Medicine in Baltimore call for better reporting to help understand the scale of this problem and determine how to tackle it.
Currently, death certification in the U.S. relies on assigning an International Classification of Disease (ICD) code to the cause of death, so causes of death not associated with an ICD code, such as human and system factors, are not captured. According to the World Health Organization, 117 countries code their mortality statistics using the ICD system, including the UK and Canada.
As a result, accurate data on deaths associated with medical error is lacking. However, using studies from 1999 onwards — and extrapolating to the total number of U.S. hospital admissions in 2013 — Makary and Daniel calculated a mean rate of death from medical error of 251,454 a year.
Comparing their estimate to the annual list of the most common causes of death in the U.S., compiled by the Centers for Disease Control and Prevention (CDC), suggests that medical error is the third most common cause of death in the US.
Fixing medical errors
“Although we cannot eliminate human error, we can better measure the problem to design safer systems mitigating its frequency, visibility, and consequences,” the experts advise, using three steps: making errors more visible when they occur so their effects can be intercepted; having remedies at hand to rescue patients; and making errors less frequent by following principles that take human limitations into account.
For instance, instead of simply requiring cause of death, they suggest that death certificates could contain an extra field asking whether a preventable complication stemming from the patient’s medical care contributed to the death. Another strategy would be for hospitals to carry out a rapid and efficient independent investigation into deaths to determine the potential contribution of error.
Measuring the consequences of medical care on patient outcomes “is an important prerequisite to creating a culture of learning from our mistakes, thereby advancing the science of safety and moving us closer towards creating learning health systems,” they add.
“Sound scientific methods, beginning with an assessment of the problem, are critical to approaching any health threat to patients,” they write. “The problem of medical error should not be exempt from this scientific approach.”
And they call for “more appropriate recognition of the role of medical error in patient death to heighten awareness and guide both collaborations and capital investments in research and prevention.”
Abstract of Medical error—the third leading cause of death in the US
The annual list of the most common causes of death in the United States, compiled by the Centers for Disease Control and Prevention (CDC), informs public awareness and national research priorities each year. The list is created using death certificates filled out by physicians, funeral directors, medical examiners, and coroners. However, a major limitation of the death certificate is that it relies on assigning an International Classification of Disease (ICD) code to the cause of death.1 As a result, causes of death not associated with an ICD code, such as human and system factors, are not captured. The science of safety has matured to describe how communication breakdowns, diagnostic errors, poor judgment, and inadequate skill can directly result in patient harm and death. We analyzed the scientific literature on medical error to identify its contribution to US deaths in relation to causes listed by the CDC.
Improved muscle stem cell numbers and muscle function in NR-treated aged mice: Newly regenerated muscle fibers 7 days after muscle damage in aged mice (left: control group; right: fed NR). (Scale bar = 50 μm). (credit: Hongbo Zhang et al./Science)
EPFL researchers have restored the ability of mice organs to regenerate and extend life by simply administering nicotinamide riboside (NR) to them.
NR has been shown in previous studies to be effective in boosting metabolism and treating a number of degenerative diseases. Now, an article by PhD student Hongbo Zhang published in Science also describes the restorative effects of NR on the functioning of stem cells for regenerating organs.
As in all mammals, as mice age, the regenerative capacity of certain organs (such as the liver and kidneys) and muscles (including the heart) diminishes. Their ability to repair them following an injury is also affected. This leads to many of the disorders typical of aging.
Mitochondria —> stem cells —> organs
To understand how the regeneration process deteriorates with age, Zhang teamed up with colleagues from ETH Zurich, the University of Zurich, and universities in Canada and Brazil. By using several biomarkers, they were able to identify the molecular chain that regulates how mitochondria — the “powerhouse” of the cell — function and how they change with age. “We were able to show for the first time that their ability to function properly was important for stem cells,” said Auwerx.
Under normal conditions, these stem cells, reacting to signals sent by the body, regenerate damaged organs by producing new specific cells. At least in young bodies. “We demonstrated that fatigue in stem cells was one of the main causes of poor regeneration or even degeneration in certain tissues or organs,” said Zhang.
How to revitalize stem cells
Which is why the researchers wanted to “revitalize” stem cells in the muscles of elderly mice. And they did so by precisely targeting the molecules that help the mitochondria to function properly. “We gave nicotinamide riboside to 2-year-old mice, which is an advanced age for them,” said Zhang.
“This substance, which is close to vitamin B3, is a precursor of NAD+, a molecule that plays a key role in mitochondrial activity. And our results are extremely promising: muscular regeneration is much better in mice that received NR, and they lived longer than the mice that didn’t get it.”
Parallel studies have revealed a comparable effect on stem cells of the brain and skin. “This work could have very important implications in the field of regenerative medicine,” said Auwerx. This work on the aging process also has potential for treating diseases that can affect — and be fatal — in young people, like muscular dystrophy (myopathy).
So far, no negative side effects have been observed following the use of NR, even at high doses. But while it appears to boost the functioning of all cells, it could include pathological ones, so further in-depth studies are required.
Abstract of NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice
Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) and its impact on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD+ precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response (UPRmt) and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the Mdx mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs (NSCs) and melanocyte SCs (McSCs), and increased mouse lifespan. Strategies that conserve cellular NAD+ may reprogram dysfunctional SCs and improve lifespan in mammals.
The STAR robot suturing intestinal tissue (credit: Azad Shademan et al./Science Translational Medicine)
Can a robot handle the slippery stuff of soft tissues that can move and change shape in complex ways as stitching goes on, normally requiring a surgeon’s skill to respond to these changes to keep suturing as tightly and evenly as possible?
A Johns Hopkins University and Children’s National Health System research team decided to find out by using their “Smart Tissue Autonomous Robot” (STAR) to perform in a procedure called anastomosis* (joining two tubular structures such as blood vessels together), using pig intestinal tissue.
The researchers published the results today in an open-access paper in the journal Science Translational Medicine. The robot surgeon took longer (up to 57 minutes vs. 8 minutes for human surgeons) but “the machine does it better,” according to Peter Kim, M.D., Professor of Surgery at the Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System in Washington D.C. Kim said the procedure was about 60 percent fully autonomous and 40 percent supervised (“we made some minor adjustments”), but that it can be made fully autonomous.
“The equivalent of a fancy sewing machine”
Automating soft tissue surgery. Left: The STAR system integrates near-infrared fluorescent (NIRF) imaging of markers (added by the surgeon to allow STAR to track surgical motions through blood and tissue occlusions), 3D plenoptic vision (captures the intensity and direction of the light rays emanating from the markers), force sensing, submillimeter positioning, and actuated surgical tools. Right: surgical site detail during linear suturing task showing a longitudinally cut porcine intestine suspended by five stay sutures. (credit: Azad Shademan et al./Science Translational Medicine)
STAR was developed by Azad Shademan and associates at the Sheikh Zayed Institute. It features a 3D imaging system and a near-infrared sensor to spot fluorescent markers along the edges of the tissue to keep the robotic suture needle on track. Unlike most other robot-assisted surgical systems, such as the Da Vinci Si, it operates without human hands-on guidance (but under the surgeon’s supervision).
In the research, the STAR robotic sutures were compared with the work of five surgeons completing the same procedure using three methods: open surgery, laparoscopic, and robot assisted surgery. Researchers compared consistency of suture spacing, pressure at which the seam leaked, mistakes that required removing the needle from the tissue or restarting the robot, and completion time.
The system promises to improve results for patients and make the best surgical techniques more widely available, according to the researchers. Putting a robot to work in this form of surgery “really levels the playing field,” said Simon Leonard, a computer scientist an assistant research professor in the Johns Hopkins Whiting School of Engineering, who worked for four years to program the robotic arm to precisely stitch together pieces of soft tissue.
As Leonard put it, they’re designing an advanced surgical tool, “the equivalent of a fancy sewing machine.”
* Anastomosis is performed more than a million times a year in the U.S.; more than 44.5 million such soft-tissue surgeries are performed in the U.S. each year. According to the researchers, complications such as leakage along the seams occur nearly 20 percent of the time in colorectal surgery and 25 to 30 percent of the time in abdominal surgery.
Carla Schaffer/AAAS | Robotic Surgery Just Got More Autonomous
Abstract of Supervised autonomous robotic soft tissue surgery
The current paradigm of robot-assisted surgeries (RASs) depends entirely on an individual surgeon’s manual capability. Autonomous robotic surgery—removing the surgeon’s hands—promises enhanced efficacy, safety, and improved access to optimized surgical techniques. Surgeries involving soft tissue have not been performed autonomously because of technological limitations, including lack of vision systems that can distinguish and track the target tissues in dynamic surgical environments and lack of intelligent algorithms that can execute complex surgical tasks. We demonstrate in vivo supervised autonomous soft tissue surgery in an open surgical setting, enabled by a plenoptic three-dimensional and near-infrared fluorescent (NIRF) imaging system and an autonomous suturing algorithm. Inspired by the best human surgical practices, a computer program generates a plan to complete complex surgical tasks on deformable soft tissue, such as suturing and intestinal anastomosis. We compared metrics of anastomosis—including the consistency of suturing informed by the average suture spacing, the pressure at which the anastomosis leaked, the number of mistakes that required removing the needle from the tissue, completion time, and lumen reduction in intestinal anastomoses—between our supervised autonomous system, manual laparoscopic surgery, and clinically used RAS approaches. Despite dynamic scene changes and tissue movement during surgery, we demonstrate that the outcome of supervised autonomous procedures is superior to surgery performed by expert surgeons and RAS techniques in ex vivo porcine tissues and in living pigs. These results demonstrate the potential for autonomous robots to improve the efficacy, consistency, functional outcome, and accessibility of surgical techniques.
HD video transmission through human tissue from implanted medical devices via in-body ultrasonic communications: beef liver and pork loin were used to represent the density and moisture content found in human tissue (credit: UIUC)(credit: UIUC)
University of Illinois at Urbana-Champaign engineers have demonstrated real-time video-rate (>30Mbps) “meat comm” data transmission through tissue, which could mean in-body ultrasonic communications may be possible for implanted medical devices, including hi-def video.
For example, a patient could swallow a miniaturized HD video camera that could stream live to an external screen, with the orientation of the device controlled wirelessly and externally by a physician, according to Andrew Singer, the Fox Family Professor in the Department of Electrical and Computer Engineering at Illinois,
“To our knowledge, this is the first time anyone has ever sent such high data rates through animal tissue,” Singer added. “These data rates are sufficient to allow real-time streaming of high definition video, enough to watch Netflix, for example, and to operate and control small devices within the body.”
Ingestible cameras and other devices
Potential biomedical uses include ingestible cameras for imaging the digestive track, as well as lower-bandwidth devices such as implanted pacemakers and defibrillators, glucose monitors and insulin pumps, intracranial pressure sensors, and epilepsy control.
Currently, most implanted medical devices use RF electromagnetic waves to communicate through the body. The Federal Communications Commission (FCC) regulates the bandwidths that can be used for RF electromagnetic wave propagation available to implanted medical devices. For example, the Medical Device Radiocommunication Service (MDRS) designates frequencies of operation ranging from 401–406 MHz (where these is high absorption). The corresponding maximum bandwidth allowed is 300 kHz and a maximum of 50 kb/s.
The main limitation for using RF electromagnetic waves in the body is loss of signal that occurs because of attenuation in the body. That requires higher power, which can cause tissue damage from heating due to absorption.
“For underwater applications, radio-frequency (RF) electromagnetic communications has long since been supplanted by acoustic communication,” Singer noted. “Acoustic or ultrasonic communication is the preferred communication means underwater because sound (pressure) waves exhibit dramatically lower losses than RF and can propagate tremendous distances for signals of modest bandwidth.”
The study was reported in an open-access paper on arXiv.org. The researchers have received a provisional patent application on the high-definition ultrasonic technology. They will be presenting their findings at the 17th IEEE International Workshop on Signal Processing Advances in Wireless Communications, this July in Edinburgh, UK.
Abstract of Mbps Experimental Acoustic Through-Tissue Communications: MEAT-COMMS
Methods for digital, phase-coherent acoustic communication date to at least the work of Stojanjovic, et al [20], and the added robustness afforded by improved phase tracking and compensation of Johnson, et al [21]. This work explores the use of such methods for communications through tissue for potential biomedical applications, using the tremendous bandwidth available in commercial medical ultrasound transducers. While long-range ocean acoustic experiments have been at rates of under 100kbps, typically on the order of 1- 10kbps, data rates in excess of 120Mb/s have been achieved over cm-scale distances in ultrasonic testbeds [19]. This paper describes experimental transmission of digital communication signals through samples of real pork tissue and beef liver, achieving data rates of 20-30Mbps, demonstrating the possibility of real-time video-rate data transmission through tissue for inbody ultrasonic communications with implanted medical devices.
Researchers at McMaster University have found that a single minute of very intense exercise within a 10-minute session produces health benefits similar to those from 50 minutes of moderate-intensity continuous exercise.
Brief bursts of intense exercise are remarkably effective, a very time-efficient workout strategy, according to Martin Gibala, a professor of kinesiology at McMaster and lead author on the study, published online in an open-access paper in the journal PLOS ONE
Gibala and associates compared their “sprint interval training” (SIT) protocol to moderate-intensity continuous training (MICT), which is recommended in current public-health guidelines. They examined key health indicators, including insulin sensitivity (a measure of how the body regulates blood sugar) and cardiorespiratory fitness.
Quick intense vs. longer moderate
The ”sprint interval training” (SIT) protocol in the experiment involved three intermittent 20-second “all-out” cycle sprints interspersed with two minutes of continuous low-intensity exercise for recovery. MICT (the current exercise guideline) involves 45 minutes of continuous cycling at ~70% maximal heart rate. Both protocols involve a two-minute warm-up and three-minute cool-down.
In the experiment, a total of 27 sedentary men were recruited and assigned to perform three weekly sessions of either intense or moderate training for 12 weeks, or to a control group that did not exercise.
After 12 weeks of training, the results were remarkably similar, even though the MICT protocol involved five times as much exercise and a five-fold greater time commitment. Specifically, the researchers found a strikingly similar 19% improvement in cardiorespiratory fitness as determined by peak oxygen uptake (VO2 peak), which compares favorably with the typical change reported after several months of traditional endurance training (MICT).
“Most people cite ‘lack of time’ as the main reason for not being active,” says Gibala. “Our study shows that an interval-based approach can be more efficient — you can get health and fitness benefits comparable to the traditional approach, in less time. The basic principles apply to many forms of exercise. Climbing a few flights of stairs on your lunch hour can provide a quick and effective workout. The health benefits are significant.”
This project was supported by an operating grant from the Natural Sciences and Engineering Research Council, and an internally-sponsored research grant from McMaster University to MJG.
McMaster | Gibala on HIIT
Abstract of Twelve Weeks of Sprint Interval Training Improves Indices of Cardiometabolic Health Similar to Traditional Endurance Training despite a Five-Fold Lower Exercise Volume and Time Commitment
Aims: We investigated whether sprint interval training (SIT) was a time-efficient exercise strategy to improve insulin sensitivity and other indices of cardiometabolic health to the same extent as traditional moderate-intensity continuous training (MICT). SIT involved 1 minute of intense exercise within a 10-minute time commitment, whereas MICT involved 50 minutes of continuous exercise per session.
Methods: Sedentary men (27±8y; BMI = 26±6kg/m2) performed three weekly sessions of SIT (n = 9) or MICT (n = 10) for 12 weeks or served as non-training controls (n = 6). SIT involved 3×20-second ‘all-out’ cycle sprints (~500W) interspersed with 2 minutes of cycling at 50W, whereas MICT involved 45 minutes of continuous cycling at ~70% maximal heart rate (~110W). Both protocols involved a 2-minute warm-up and 3-minute cool-down at 50W.
Results: Peak oxygen uptake increased after training by 19% in both groups (SIT: 32±7 to 38±8; MICT: 34±6 to 40±8ml/kg/min; p<0.001 for both). Insulin sensitivity index (CSI), determined by intravenous glucose tolerance tests performed before and 72 hours after training, increased similarly after SIT (4.9±2.5 to 7.5±4.7, p = 0.002) and MICT (5.0±3.3 to 6.7±5.0 x 10−4 min-1[μU/mL]-1, p = 0.013) (p<0.05). Skeletal muscle mitochondrial content also increased similarly after SIT and MICT, as primarily reflected by the maximal activity of citrate synthase (CS; P<0.001). The corresponding changes in the control group were small for VO2peak (p = 0.99), CSI (p = 0.63) and CS (p = 0.97).
Conclusions: Twelve weeks of brief intense interval exercise improved indices of cardiometabolic health to the same extent as traditional endurance training in sedentary men, despite a five-fold lower exercise volume and time commitment.
