Improvements in optical mammography to advance breast cancer diagnostics

Researchers from Politecnico di Milano, Italy report improvements in the design of optical mammography used in diagnosis and monitoring of breast cancer.  They report increase sensitivity by a thousandfold.This research is presented at Biomedical Optics meeting 2018.

Schematic diagram of new and improved optical mammography device.
Credit: Edoardo Ferocino

Optical mammography uses infrared light and is used in conjunction with x-rays. It is optimal in cases needing repeated imaging to prevent high amounts of radiation associated with the regular procedure. Optical mammography can be used to measure blood volume, oxygenation, lipid, water and collagen content for a suspicious area identified through standard X-ray imaging. However, there are limitations to using optical mammography, which includes poor spatial resolution.

New improvements include using eight channel silicon photomultipliers (SiPMs) and multichannel time-to-digital converter instead of two photomultiplier tubes (PMTs) in existing optical mammography instruments. These changes eliminate the pre-scan step that was required to avoid damage to the photomultiplier tubes. In addition to increased sensitivity, the new instrument is both more robust and cheaper.

The investigators in Milan are working with a larger consortium on a project known as SOLUS, “Smart Optical and Ultrasound Diagnostics of Breast Cancer.” This project is funded by the European Union through the Horizon 2020 Research and Innovation Program and aims to combine optical imaging methods with ultrasound to improve specificity in the diagnosis of breast cancer.

Adapted from press release by the Optical Society.

Smartphone app to reliably diagnose irregular heartbeat or atrial fibrillation

Researchers from the University of Turku developed a smartphone app to detect atrial fibrillation with phone alone, without any extra equipment. This application provides a potential tool for timely diagnosis of atrial fibrillation as it is crucial for effective stroke prevention. The results of the study were published in the journal Circulation.

Smartphone app to detect atrial fibrillation or irregular heartbeat.
Credit: Hannah Oksanen, University of Turku.

Researchers conducted a study on three hundred patients with heart problems, 50% had atrial fibrillation. The researchers managed to identify the patients with atrial fibrillation from the other group with a smartphone with around 96% accuracy. According to Chief Physician and Professor of Cardiology Juhani Airaksinen from Turku University Hospital, this is the first time that ordinary consumer electronics have achieved such reliable results.

The technology behind the application involves using small accelerometers that are present in most smartphones. Researchers call this technique mechanochardiography, as it uses mechanical stimulus to generate heart trace.

The researchers want to make this app available for all as quickly as possible. According to Mr. Koivisto, the commercialization of the method is advancing quickly.

Reference: Jaakkola, Jussi, Samuli Jaakkola, Olli Lahdenoja, Tero Hurnanen, Tero Koivisto, Mikko Pänkäälä, Timo Knuutila, Tuomas O. Kiviniemi, Tuija Vasankari, and K.e. Juhani Airaksinen. “Mobile Phone Detection of Atrial Fibrillation With Mechanocardiography: The MODE-AF Study (Mobile Phone Detection of Atrial Fibrillation).” Circulation, 2018. doi:10.1161/circulationaha.117.032804.

Adapted from press release by the University of  Turku.

Researchers develop ultra thin wearable skin electronics

This latest research by a Japanese academic-industrial collaboration, led by Professor Takao Someya at the University of Tokyo’s Graduate School of Engineering presents a new ultrathin, elastic display that fits snugly on the skin and can show the moving waveform of an electrocardiogram recorded by a breathable, on-skin electrode sensor. Combined with a wireless communication module, this integrated biomedical sensor system called “skin electronics” can transmit biometric data to the cloud.

Wearable skin electronic biosensors. Credit: 2018 Takao Someya Research Group.

The new integrated system combines a flexible, deformable display with a lightweight sensor composed of a breathable nanomesh electrode and wireless communication module. Medical data measured by the sensor, such as an electrocardiogram, can either be sent wirelessly to a smartphone for viewing or to the cloud for storage. In the latest research, the display showed a moving electrocardiogram waveform that was stored in memory.

The skin display, developed by a collaboration between researchers at the University of Tokyo’s Graduate School of Engineering and Dai Nippon Printing (DNP), a leading Japanese printing company, consists of a 16 x 24 array of micro LEDs and stretchable wiring mounted on a rubber sheet.

“Our skin display exhibits simple graphics with motion,” says Someya. “Because it is made from thin and soft materials, it can be deformed freely.” The display is stretchable by as much as 45 percent of its original length. It is far more resistant to the wear and tear of stretching than previous wearable displays. It is built on a novel structure that minimizes the stress resulting from stretching on the juncture of hard materials, such as the micro LEDs, and soft materials, like the elastic wiring a leading cause of damage for other models.

The nanomesh skin sensor can be worn on the skin continuously for a week without causing any inflammation. Although this sensor, developed in an earlier study, was capable of measuring temperature, pressure and myoelectricity (the electrical properties of muscle), it successfully recorded an electrocardiogram for the first time in the latest research.

The researchers applied tried-and-true methods used in the mass production of electronics – specifically, screen printing the silver wiring and mounting the micro LEDs on the rubber sheet with a chip mounter and solder paste commonly used in manufacturing printed circuit boards. DNP is looking to bring the integrated skin display to market within the next three years by improving the reliability of the stretchable devices through optimizing its structure, enhancing the production process for high integration, and overcoming technical challenges such as large-area coverage.

“The current aging society requires user-friendly wearable sensors for monitoring patient vitals in order to reduce the burden on patients and family members providing nursing care,” says Someya. “Our system could serve as one of the long-awaited solutions to fulfill this need, which will ultimately lead to improving the quality of life for many.”

Adapted from press release by the University of Tokyo.

Big data from smart thermometer utilized to track and predict flu activity.

A study by researchers at the University of Iowa shows that anonymous data from a “smart thermometer” connected to a mobile phone app can track flu activity in real time at both population and individual levels. They also showed that this data can be used to improve flu forecasting. The study findings are published in the journal Clinical Infectious Diseases.

“We found the smart thermometer data are highly correlated with information obtained from traditional public health surveillance systems and can be used to improve forecasting of influenza-like illness activity, possibly giving warnings of changes in disease activity weeks in advance,” says lead study author Aaron Miller, PhD, a UI postdoctoral scholar in computer science. “Using simple forecasting models, we showed that thermometer data could be effectively used to predict influenza levels up to two to three weeks into the future. Given that traditional surveillance systems provide data with a lag time of one to two weeks, this means that estimates of future flu activity may actually be improved up to four or five weeks earlier.”

Miller and senior study author Philip Polgreen, MD, UI associate professor of internal medicine and epidemiology, analyzed de-identified data from the commercially available Kinsa Smart Ear Thermometers and accompanying app, which recorded users’ temperature measurement over a study period from Aug. 30, 2015 to Dec. 23, 2017. There were over 8 million temperature readings generated by almost 450,000 unique devices. The smart thermometers encrypt device identities to protect user privacy and also give users the option of providing anonymized information on age or sex. Readings were reported from all 50 states and were aggregated to provide region and age-group specific flu activity estimates.

The UI team compared the data from the smart thermometers to influenza-like illness (ILI) activity data gathered by the Centers for Disease Control and Prevention (CDC) from health care providers across the country. They found that the de-identified smart thermometer data was highly correlated with ILI activity at national and regional levels and for different age groups.

Current forecasts rely on this CDC data, but even at its fastest, the information is almost two weeks behind real-time flu activity. The UI study showed that adding thermometer data, which captures clinically relevant symptoms (temperature) likely even before a person goes to the doctor, to simple forecasting models, improved predictions of flu activity. This approach accurately predicted influenza activity at least three weeks in advance.

Miller notes that the smart thermometers also provide a way to estimate which age groups are being most affected during a flu season, using de-identified data. Monitoring the duration of fever from the smart thermometer readings also revealed that fevers occurring during flu season were more likely to last three to six days and much less likely to last only one day. Fevers lasting even or more days were not at all seasonal. The data also identified instances where users had fever that went away for a few days and then returned. The researchers believe this so-called “biphasic” fever pattern may reflect more serious illnesses. The second temperature spike can indicate a secondary bacterial infection like pneumonia that sets in after the flu and can lead to more severe health problems, especially in older individuals.

Citation:  Miller, Aaron C., Inder Singh, Erin Koehler, and Philip M. Polgreen. “A Smartphone-Driven Thermometer Application for Real-Time Population- and Individual-Level Influenza Surveillance.” Clinical Infectious Diseases, 2018. doi:10.1093/cid/ciy073.

Adapted from press release by  University of Iowa.

Glassy carbon electrodes advances brain-computer interface technology

The Center for Sensorimotor Neural Engineering-a collaboration of San Diego State University with the University of Washington and the Massachusetts Institute of Technology is working on an implantable brain chip that can record neural electrical signals and transmit them to receivers in the limb. Results of the research study utilizing above technology are published in the journal Nature Scientific Reports.

Glassy Carbon Electrodes for Brain-computer Interface technology
This image shows a sheet of glassy carbon electrodes patterned inside chips.
Credit: Sam Kassegne, San Diego State University.

When people suffer spinal cord injuries and lose mobility in their limbs, the brain can still send clear electrical impulses and the limbs can still receive them, but the signal gets lost in the damaged spinal cord. The brain chip the researchers works by bypassing the damage and restoring movement.

The technology, known as a brain-computer interface, records and transmits signals through electrodes, which are tiny pieces of material that read signals from brain chemicals known as neurotransmitters. The device works by recording and analyzing brain signals and convert them into a relevant electrical signal pattern, these signals are then transmitted to the limb’s nerves, or even to a prosthetic limb, restoring mobility and motor function.

The current state-of-the-art material for electrodes in these devices is thin-film platinum. The problem is that these electrodes can fracture and fall apart over time, said one of the study’s lead investigators, Sam Kassegne, deputy director for the CSNE at SDSU and a professor in the mechanical engineering department. To overcome this problem researchers developed electrodes made out of glassy carbon, a form of carbon. This material is about 10 times smoother than granular thin-film platinum, meaning it corrodes less easily under electrical stimulation and lasts much longer than platinum or other metal electrodes. Researchers are using these new and improved brain-computer interfaces to record neural signals both along the brain’s cortical surface and from inside the brain at the same time.

A doctoral graduate student in Kassegne’s lab, Mieko Hirabayashi, is exploring a slightly different application of this technology. She’s working with rats to find out whether precisely calibrated electrical stimulation using these electrodes can cause new neural growth within the spinal cord with hope to replicate these results in humans. The new glassy carbon electrodes will allow her to stimulate, read the electrical signals of and detect the presence of neurotransmitters in the spinal cord better than ever before.

Citation: Vomero, Maria, Elisa Castagnola, Francesca Ciarpella, Emma Maggiolini, Noah Goshi, Elena Zucchini, Stefano Carli, Luciano Fadiga, Sam Kassegne, and Davide Ricci. “Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity.” Scientific Reports 7 (2017): 40332.
DOI:10.1038/srep40332.
Research funding: National Science Foundation.
Adapted from press release by San Diego State University.

Research shows reduced Surgical Site Infections with use of Antimicrobial Sutures

New analyses of the published clinical studies indicate that antimicrobial sutures are effective for preventing surgical site infections (SSIs), and they can result in significant cost savings. The results are published in the British Journal of Surgery.

In one analysis that included 21 randomized clinical trials, investigators found a risk of 138 surgical site infections per 1000 procedures, and the use of sutures coated with the antimicrobial triclosan reduced this by 39. Investigators noted that sufficient evidence exists for a 15 percent relative risk reduction in SSIs when triclosan-coated sutures are used.

In an economic analysis of results from 34 studies, triclosan sutures were linked with an average cost savings per surgical procedure of  91.25 pounds across all wound classes when compared with non-antimicrobial-coated sutures.

“Antimicrobial sutures ought to be included into SSI care bundles and provide a further significant saving to National Health Service (England) surgical practice,” said Prof. David Leaper, lead author of the economic analysis.

Citations:

S. W. de Jonge, J. J. Atema, J. S. Solomkin and M. A. Boermeester. Meta-analysis and trial sequential analysis of triclosan-coated sutures for the prevention of surgical-site infection. British Journal of Surgery.
DOI: 10.1002/bjs.10445

D. J. Leaper, C. E. Edmiston Jr and C. E. Holy. Meta-analysis of the potential economic impact following introduction of absorbable antimicrobial sutures. British Journal of Surgery.
DOI: 10.1002/bjs.10443

Adapted from press release by Wiley publications.

Painless skin patch created with flexible base and stainless steel microneedles

It’s only a matter of time before drugs are administered via patches with painless microneedles instead of unpleasant injections. But designers need to balance the need for flexible, comfortable to wear material with effective microneedle penetration of the skin. Researchers from KTH Royal Institute of Technology in Stockholm say they may have cracked the problem.

A flexible base, combined with stainless steel needles, could make the patch created at KTH an effective alternative to injections. Credit: KTH Royal Institute of Technology.

In a study published in PLOS ONE, the research team from KTH reports a successful test of its microneedle patch, which combines stainless steel needles embedded in a soft polymer base – the first such combination believed to be scientifically studied. The soft material makes it comfortable to wear, while the stiff needles ensure reliable skin penetration.

Unlike epidermal patches, microneedles penetrate the upper layer of the skin, just enough to avoid touching the nerves. This enables delivery of drugs, extraction of physiological signals for fitness monitoring devices, extracting body fluids for real-time monitoring of glucose, pH level and other diagnostic markers, as well as skin treatments in cosmetics and bioelectric treatments.

Frank Niklaus, professor of micro and nanofabrication at KTH, says that practically all microneedle arrays being tested today are “monoliths”, that is, the needles and their supporting base are made of the same – often hard and stiff – material. While that allows the microneedles to penetrate the skin, they are uncomfortable to wear. On the other hand, if the whole array is made from softer materials, they may fit more comfortably, but soft needles are less reliable for penetrating the skin.

“To the best of our knowledge, flexible and stretchable patches with arrays of sharp and stiff microneedles have not been demonstrated to date,” he says.

They actually tested two variations of their concept, one which was stretchable and slightly more flexible than the other. The more flexible patch, which has a base of molded thiol-ene-epoxy-based thermoset film, conformed well to deformations of the skin surface and each of the 50 needles penetrated the skin during a 30 minute test.

A successful microneedle product could have major implications for health care delivery. “The chronically ill would not have to take daily injections,” says co-author Niclas Roxhed, who is research leader at the Department of Micro and Nanotechnology at KTH.

In addition to addressing people’s reluctance to take painful shots, microneedles also offer a hygiene benefit. The World Health Organization estimates that about 1.3 million people die worldwide each year due to improper handling of needles. “Since the patch does not enter the bloodstream, there is less risk of spreading infections,” Roxhed says.

Citation: Rajabi, Mina, Niclas Roxhed, Reza Zandi Shafagh, Tommy Haraldson, Andreas Christin Fischer, Wouter van der Wijngaart, Göran Stemme, and Frank Niklaus. “Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.” PLOS ONE 11, no. 12 (2016): e0166330.
DOI: 10.1371/journal.pone.0166330
Adapted from press release by KTH Royal Institute of Technology.

Carbon nanotube based electrical immunosensor to rapidly detect troponin I during a heart attack

Heart disease is the leading cause of death for both men and women. Therefore, a fast and reliable diagnosis of heart attack is urgently needed. A study, led by Prof. Jaesung Jang (School of Mechanical and Nuclear Engineering) has developed an electrical immunosensor to detect the acute myocardial infarction, also known as a heart attack within a minute. The system works by measuring the level of cardiac troponin I (cTnI), a protein that is excreted by the heart muscle into the blood following a heart attack.

Image shown above is the core material used for the new immunosensor that detects proteins in the blood stream following a heart attack, providing results in just 1 minute. Credit: Uslan National Institute of Science and Technology

Prof. Jang states, “This new immunosensor is constructed in a different way than any other sensor.” He adds, “Owing to the new design of this immunosensor, this device is able to rapidly diagnose the level of heart attacks at the point of care.”

Using just a single droplet of blood, this immunosensor detects the target protein present in the blood serum following a heart attack and provides a result in 1 minute.

In the study, dielectrophoretic (DEP) forces have been applied to attract the target protein. The incubation time required for the detection is decreased through DEP-mediated biomarker concentration, in which the target protein is attracted to the sensing areas via electrical forces. Therefore, the dielectrophoretic concentration of cTnI reduced the incubation time required from 60 min to 1 min.

Chang-Ho Han (School of Mechanical and Nuclear Engineering), a combined masters doctoral student in Prof. Jang’s group notes, “The level of cTnI within a single droplet of blood serum is not great.” He continues, “However, we were able to attract the target protein onto the sensing areas via electrical forces, thereby greatly improving detection time and detection limit.”

According to the research team, this novel immunosensor holds considerable potential for use as a platform for sensing distinct types of proteins, along with the feasibility of miniaturization and integration for biomedical diagnosis.

The findings of the research have been published in biotechnology journal Biosensors & Bioelectronics.

Citation: Sharma, Abhinav, Chang-Ho Han, and Jaesung Jang. “Rapid electrical immunoassay of the cardiac biomarker troponin I through dielectrophoretic concentration using imbedded electrodes.” Biosensors and Bioelectronics 82 (2016): 78-84.
DOI: 10.1016/j.bios.2016.03.056
Research funding: National Research Foundation of Korea, Korean Ministry of Education, 2016 Research Fund of UNIST.
Adapted from press release by Uslan National Institute of Science and Technology.

Novel bio-signal measuring electrodes to advance health diagnosis using internet of things devices

Daegu Gyeongbuk Institute of Science and Technology (DGIST) announced that Professor Kyung-in Jang’s research team from the Department of Robotics Engineering succeeded in developing bio-signal measuring electrodes that can be mounted on Internet of Things (IoT) devices through joint research with a research team led by professor John Rogers of the University of Illinois, USA.

Optical image of bio-signal measurement electrode
design developed by Professor Jang’s research team.
The electrode generates such a large force that it holds
the circular magnet located under the glass only by
attraction (gravitation) of the magnetic field.
Credit: DGIST
The bio-signal measuring electrodes developed by the research team can be easily mounted onInternet of Things (IoT) devices for health diagnosis, thus they can measure bio-signals such as brain waves and electrocardiograms without additional analysis and measurement equipment while not interfering or restricting human activities.
Conventional hydro-gel based electrodes required external analysis and measurement devices to measure bio-signals due to their pulpy gel forms, which made their attachment to and detachment from IoT devices instable. In addition, since these electrodes were wet-bonded to the skin, there have been disadvantages that the characteristics of the electrodes deteriorated or their performance decreased when the electrodes were dried in the air over a long period.
In contrast, the electrodes developed by Professor Kyung-in Jang can be easily interlocked as if they are a part of Internet of Things (IoT) devices for health diagnosis. Also, since they are composed only of polymer and metal materials, they have the advantage of there being no possibility of drying in the air.

The bio-signal measurement electrodes developed by the research team consist of a composite material in which a magnetic material is folded with a soft and adhesive polymer, with a conductive electrode material wrapped around the composite material. The conductive electrode material electrically connects the bottom surface touching the skin and the top surface touching the electrode of the Internet of Things (IoT) device.

Electrodes with this structure reacting to the magnetic field can be easily attached and detached by using the attraction that occurs between the magnet and the electrode mounted on the IoT devices. Then, through the conductive electrode materials that connect the skin and the electrode part of the IoT device, the electric signals generated on the skin can be directly transmitted to the IoT device for health diagnosis.

The research team succeeded in storing and analyzing brain waves (electroencephalogram, EEG), electrocardiograms (ECG), eye movements (electrooculogram, EOG), and limb movements and muscle contractions (electromyogram, EMG) of the wearer for a long period through an experiment in which IoT devices with the electrodes are attached to various parts of the human body.

The bio-signal measurement electrodes can measure the bioelectric signal generated from the skin without loss or noise by using the Internet of Things (IoT) platform, thus they are expected to be applicable to the medical and healthcare fields since they cannot only measure the electrical signals of the body, but also analyze various forms of bio-signals such as body temperature change, skin change, and in-body ion concentration change.

Professor Kyung-in Jang said, “We have secured the source technology that can diagnose the state of human health anytime and anywhere by combining bio-electrode technology with Internet of Things (IoT) platforms utilizing advanced high-tech composite materials. We will carry out subsequent research to make it applicable for diseases that require ongoing medical diagnosis such as diabetes, insomnia, and epilepsy, and to make it available to people in medically vulnerable areas such as remote mountainous and rural areas.”

Citation: “Ferromagnetic, Folded Electrode Composite as a Soft Interface to the Skin for Long-Term Electrophysiological Recording”. Kyung-In Jang, Han Na Jung, Jung Woo Lee, Sheng Xu, Yu Hao Liu, Yinji Ma, Jae-Woong Jeong, Young Min Song, Jeonghyun Kim, Bong Hoon Kim, Anthony Banks, Jean Won Kwak, Yiyuan Yang, Dawei Shi, Zijun Wei, Xue Feng, Ungyu Paik, Yonggang Huang, Roozbeh Ghaffari, John A. Rogers.Advanced Functional Materials 2016 vol: 26 (40) pp: 7281-7290.
DOI: 10.1002/adfm.201603146
Adapted from press release by Daegu Gyeongbuk Institute of Science and Technology (DGIST).

New technology using gold wires on flexible plastic for wearable electronic devices

Researchers from National Institute of Standards and Technology (NIST) has come up with a way to build safe, nontoxic gold wires onto flexible, thin plastic film. Their demonstration potentially clears the path for a host of wearable electronic devices that monitor our health.

NIST research has found that the flexible plastic membrane on
 which wearables would be built might work better if the
membrane had microscopic holes in it.
Credit: Reyes-Hernandez/NIST
Wearable health monitors are already commonplace; bracelet-style fitness trackers have escaped mere utility to become a full-on fashion trend. But the medical field has its eye on something more profound, known as personalized medicine. The long-term goal is to keep track of hundreds of real-time changes in our bodies, from fluctuations in the amount of potassium in sweat to the level of particular sugars or proteins in the bloodstream. These changes manifest themselves a bit differently in each person, and some of them could mark the onset of disease in ways not yet apparent to a doctor’s eye. Wearable electronics might help spot those problems early.

First, though, engineers need a way to build them so that they work dependably and safely–a tall order for the metals that make up their circuits and the flexible surfaces or “substrates” on which they are built. Gold is a good option because it does not corrode, unlike most metals, and it has the added value of being nontoxic. But it’s also brittle. If you bend it, it tends to crack, potentially breaking completely– meaning thin gold wires might stop conducting electricity after a few twists of the body.

“Gold has been used to make wires that run across plastic surfaces, but until now the plastic has needed to be fairly rigid,” said Reyes-Hernandez. “You wouldn’t want it attached to you; it would be uncomfortable.”

Reyes-Hernandez doesn’t work on wearable electronics. His field is microfluidics, the study of tiny quantities of liquid and their flow, typically through narrow, thin channels. One day he was exploring a commercially available porous polyester membrane–it feels like ordinary plastic wrap, only a lot lighter and thinner–to see if its tiny holes could make it useful for separating different fluid components. He patterned some gold electrodes onto the membrane to create a simple device that would help with separations. While sitting at his desk, he twisted the plastic a few times and noticed the electrodes, which covered numerous pores as they crisscrossed the surface, still conducted electricity. This wasn’t the case with nonporous membranes. “Apparently the pores keep the gold from cracking as dramatically as usual,” he said. “The cracks are so tiny that the gold still conducts well after bending.”

Reyes-Hernandez said the porous membrane’s electrodes show even higher conductivity than their counterparts on rigid surfaces, an unexpected benefit that he cannot explain as yet. The next steps, he said, will be to test changes in conductivity over the long term after many bends and twists, and also to build some sort of sensor out of the electrode-coated membrane to explore its real-world usability. “This thin membrane could fit into very small places,” he said, “and its flexibility and high conductivity make it a very special material, almost one of a kind.”

Citation: “Flexible Thin-Film Electrodes on Porous Polyester Membranes for Wearable Sensors”.
Aveek Gangopadhyay, Brian J. Nablo, Mulpuri V. Rao,  Darwin R. Reyes. Advanced Engineering Materials 2016.
DOI: 10.1002/adem.201600592
Adapted from press release by National Institute of Standards and Technology.