
Medicine that is only skin deep
Nayanah Siva
December 2015
In our continued quest towards personalised medicine, innovators have invented a new type of “electronic skin” thinner than the foil that wraps your favourite chocolate truffle. This “skin” will be able to sense, collect, and store individualised patient physiological data wirelessly (1) but that's not all.
Plenty of biosensing wearables already exist that can assess individuals’ physiological data, and can aid doctors with diagnostics and health assessment. As a separate area, researchers are trying to advance, our already established, transdermal drug delivery technology, which nowadays consists of patches for hormonal treatment, vitamin deficiency and nicotine withdrawal. But imagine if there was a wearable as thin, and flexible, as our skin that could not only read patients health status but could deliver drugs as, and when is needed? Scientists have done just this.
Still in its early stages, researchers based in South Korea, Texas and Boston are the first to build this type of functioning epidermal sensor that can collect and store data, as well as deliver drugs directly through the skin.
“We are aiming to develop high-performance flexible and stretchable electronic devices using high quality single crystal inorganic materials integrated with novel nanomaterials,” explained the lead researcher Professor Dae-Hyeong Kim from the School of Chemical and Biological Engineering, Seoul National University, Republic of Korea (2, 3). Importance of skin
THE GOAL IS TO ONE DAY CLOSE THE SENSING-STORAGE-DIAGNOSIS-TREATMENT LOOP.
Current wearable’s in the form of wrist bands and stick-ons are rigid and are not flexible. The “electronic skin” device is an ultra-thin, ultra-soft (0.003 mm) silicon patch that can easily bond to the curvilinear surface of the skin, as a temporary transfer tattoo would do. The role of human skin is essential in measuring important physiological data from the body. “As people know, the skin can detect temperature, pressure, strain, humidity, etc. It is a window into the human body,” said Professor Kim.
The group’s patch supports electronic circuits, including multiple sensors that can convert data from multiple stimuli to a measurable signal that is transferred wirelessly explained Dr Jaemin Kim from the School of Chemical and Biological Engineering, Seoul National University, Republic of Korea. The system also contains other electrical components such as memory and actuators (that contain drug-loaded nanoparticles); and a battery is located on a separate smart band that will be connected to the electronic patch (4). The implications of this sort of technology are endless and the group envisions this sort of device being used for various disorders. “The goal is to one day close the sensing-storage-diagnosis-treatment loop”, explained Professor Nanshu Lu, Department of Aerospace Engineering and Engineering Mechanics, University of Texas, Austin, USA.
To the clinic
he multipdisciplinary group, consisting of biological and chemical engineers and nanomaterials experts are working closely with cardiologists and neurologists to understand how this type of technology can help real patients in the clinic.
Still in its infancy and currently being tested in animal models, the researchers are currently considering patients with neurological disorders. “The electronic patch is able to sense the tremor of patients with Parkinson’s Disease,” explained Dr Jaemin Kim. The patch can sense this type of movement through silicon nanoribbon-strain gauges and store the sensed frequency in the stretchable memories. The drug devices within the patch will be able to transdermally deliver treatment by using heat generated integrated thermal actuator explained Dr Kim.
“Dae-Hyeong's team is designing and fabricating the devices and performing the measurements,” said Professor Lu as she explained how the project is split up across the research group. “And my team is doing analytical and numerical modelling to understand the device mechanics and the skin-device interaction.”
A lot of the earlier generation of biosensor wearables had issues with issuing false-positives. But apparently another key advantage of the epidermal sensor, that Kim’s group pioneered, will minimise these false alarms because the sensors are so thin explained and will be immune to motion artefacts explained Professor Lu. “The sensors are so thin and so well conformed to the skin that it will not slip against the skin, even under severe skin deformation. This is a feature that is unique to epidermal sensors because conventional skin mounted sensors, including wrist bands and gel electrodes are too thick and stiff to deform together with the skin.”
Cut and paste
But there have been plenty of obstacles on the group’s journey. In this case, not with the mechanism of action and technology, but rather the manufacturing process of these epidermal sensors. The advantageous soft and thin film-like quality of the epidermal sensor means that when it is peeled off the structure crumples up making its use more appropriate as a disposable medical tool. However the microfabrication process used to manufacture the patch is expensive and time consuming, using UV light to create electronics in a mould. So Lu and her team invented a new “cut-and-paste” process that will allow them to cut electrical patterns required for the patch from thin metallic sheets, which can then be transferred onto the final substrate, which will become the patch. This new epidermal patch will cost less than $5 each, which is about ten times cheaper than using the conventional method.
“The cut-and-paste method we recently invented is a fundamentally different manufacturing process that is much more labour and cost efficient”, explained Professor Lu. “It employs cutter plotters to form patterns (which is a dry, bench top and freeform process) instead of conventional photolithography process, which requires preformed photo masks and expensive cleanroom facilities. Plus our “cut-and-paste” process does not require any rigid wafers, so it is intrinsically compatible with the low cost roll-to-roll process.” The research group will be using this process to produce the next generation of their epidermal device.
What next?
The team’s next step is to continue development of this new generation of “electronic skin” they have developed with their new “cut-and-paste” process. They want to use a more complicated array of biosensors that will match real mechanosenory and thermosensory functions that the human skin performs and will allow for more comprehensive biometric sensing. The group wants to advance to testing in larger animals and human subjects and to enhance the feedback loop of sensing and actuating targeted drug delivery.
Professor Lu explains that there is potential for this type of technology to be moved inside the body and sticking the patch to organs such as the brain, spinal cord and heart. This will be a challenge but a group at Northwestern University is making great progress, “it is a much harsher environment inside the body compared to the epidermal condition.”
Inspiration
And what keeps these innovators ticking? Professor Lu, who was named one of the world’s 35 innovators under 35 by MIT Technology Review in 2012, said she loves the field she works in. “It is full of multidisciplinary challenges and it connects fundamental science to significant social needs. I get to work with brilliant students, professors and entrepreneurs with very different backgrounds and expertise and learn from, and get inspired by them everyday. I hope my research can positively impact everyone’s everyday life.”
References
Adv. Healthcare Mater. DOI: 10.1002/adhm.201500285, 2015
Son D, Lee J, Qiao S, et al. Multifunctional wearable devices for diagnosis and therapy of movement disorders. Nature Nanotechnology; 2014 9: 397-404 DOI: 10.1038/NNANO.2014.38
Yang S, Ying-Chen c, Nicolini L, et al. “Cut-and-paste” manufacture of multiparametric epidermal sensor systems. Advanced Materials 2015 DOI: 10.1002/adma.201502386
Adv. Healthcare Mater. DOI: 10.1002/adhm.201500285, 2015
http://www.nature.com/news/electronic-skin-equipped-with-memory-1.14952
http://www.smithsonianmag.com/innovation/tiny-tattoo-wearables-could-monitor-your-health-180956862/?no-ist
http://www.sciencemag.org/content/333/6044/838.abstract
https://www.ae.utexas.edu/news/features/nanshu-lu-recognized-as-top-innovator
Sensors 2010, 10, 4558-4576; doi:10.3390/s100504558
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711927/