Glucose monitoring no sweat for new biosensors

Diabetics perform regular pinprick blood tests to monitor their glucose levels, which is both invasive and only provides a snapshot view. Imagine, instead, a noninvasive, continuous monitor that patients could wear to provide real-time tracking of glucose levels. Two recent reports bring that possibility a step closer by detecting glucose in tears and sweat.

Researchers from Ulsan National Institute of Science and Technology (UNIST) and Sungkyunkwan University in South Korea have developed a soft, smart contact lens that detects glucose levels wirelessly and noninvasively from tears [Park et al., Science Advances 4 (2018) eaap9841]. Moreover, the lens incorporates an LED display that alerts the wearer if glucose levels stray outside of healthy limits.

“Previous studies of smart contact lenses were based on rigid electronic devices on hard, plastic substrates, which offered limited comfort and wearing time for users,” says Jang-Ung Park of UNIST, who led the work. “We fabricated stretchable structures of electronic devices and stretchable circuits, including LED displays, and embedded them together in a soft contact lens.”

The device comprises an antenna for wireless power transfer, rectifier, glucose sensor, and LED linked by a network of stretchable interconnects fabricated from silver nanofibers (AgNFs), which are both highly conductive and transparent, all embedded in a flexible, biocompatible polymer lens. The AgNF antenna receives radio frequency (RF) AC signal to power the device. The rectifier converts the AC signal into DC to operate the glucose sensor and LED. The sensor is functionalized with the enzyme glucose oxidase (GOD), which oxidizes any glucose it comes into contact with in tears, changing the resistance of the device and turning the LED on or off.

“The LED display allows the user to recognize their health state (glucose level) via the LED without the need for complex measuring devices and data analysis,” explains Park.

The contact lens system also transmits detected glucose levels to a wireless display so that the wearer can monitor their health state easily without the need for bulky measuring devices. The only downside, admit the researchers, is that the system cannot currently provide quantitative glucose level values.

“Since the fabrication process of our smart lens is relatively cheap and simple, commercialization could be achieved within five years,” says Park.

But the possibilities don’t stop at glucose monitoring. Tears contain many other disease markers, which the researchers believe could also be monitored in real-time using smart lenses.

Meanwhile, a team of researchers from the University of Southern California, University of California, Los Angeles, Center of Excellence for Green Nanotechnologies, University of Jeddah, and King Abdulaziz University in Saudi Arabia report another highly sensitive sensor that could be incorporated into contact lenses or other devices such as watch straps or patches to detect glucose levels from sweat [Liu et al., ACS Nano (2018), DOI: 10.1021/acsnano.7b06823].

The team replaced typical bulky Ag/AgCl or metal wire gates with highly sensitive and flexible In₂O₃ nanoribbon field-effect transistors (FETs), which can be integrated onto various substrates and devices including contact lenses, artificial skin, sweat patches, or watchstraps. Although glucose levels are much lower in tears, sweat, and saliva than blood, In₂O₃ nanoribbon FETs offer a quick enough response for real-time monitoring, high sensitivity, a wide detection range, and reliable performance, which the researchers demonstrated over a two-week timespan.

The devices consist of In₂O₃ nanoribbons with sputter-coated Au source, drain, and side gates. The source and drain electrodes were inkjet printed with the enzyme glucose oxidase, a biocompatible polymer (chitosan), and single-walled carbon nanotubes (SWNTs), which increase the sensitivity of the sensor. When glucosemolecules come into contact with the sensor, they are immobilized by the chitosan and SWNTs, reacting with the glucose oxidase to produce hydrogen peroxide (H₂O₂). In turn, the H₂O₂ is oxidized under a bias voltage to produce oxygen and H+, which ultimately affects the current in the FET.

The device is sufficiently sensitive to detect glucose concentrations typically found in human bodily fluids and has a lower detection limit than conventional electrochemical glucose sensors. The researchers believe that the devices could be incorporated into contact lenses to monitor glucose levels from tears or into on-skin sweat patches. The approach also has potential for other types of continuous health monitoring, as well as in the food and environmental areas.

“Both are really interesting advances,” comments Zhenan Bao of Stanford University and director of the Stanford Wearable Electronics Initiative (eWEAR). “They show the new possibilities enabled by stretchable and flexible electronics.”

These attributes are key to integrating electronic functions into contact lenses, as the work by Park et al. demonstrates, she points out. Similarly, Liu et al. show how making sensors flexible can open up new applications.

“In both cases, however, solving the power issue will be crucial to take these technologies forward in the future,” Bao cautions.

This article was originally published in Nano Today 19 (2018) 1-2.