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Nanotechnology

Graphene-based wearable electronic patch for diabetes control

A graphene-based electronic patch monitors glucose in sweat noninvasively and provides feedback-controlled drug delivery by using microneedles with a heat-responsive coating.

29 June 2016, SPIE Newsroom. DOI: 10.1117/2.1201605.006498

Diabetes is one of the most prevalent chronic diseases, affecting approximately 9% of the global population. Because diabetes can cause many complications that dramatically increase the risk of death, such as cardiovascular, kidney, and neurological diseases, precise monitoring and continuous treatment are greatly needed. In the conventional treatment protocol, patients are required to take blood samples, measure the glucose concentration using a test strip together with stand-alone equipment, and then inject an appropriate amount of insulin.1 However, this process is painful, and the need for repeated blood sampling and injections causes a large amount of stress. Therefore, patients become reluctant to follow the recommended testing regime, which aggravates the symptoms of diabetes and leads to the above-mentioned complications.1

Purchase Nanotechnology: A Crash CourseRecent years have seen the emergence of wearable electronic2,3 and optoelectronic4 devices, which have opened the possibility of achieving the non-invasive control of diabetes. In particular, wearable devices for the analysis of sweat have received great attention.5–7 Human sweat contains various physiological biomarkers, including glucose. The concentration of glucose in sweat has a good correlation with the concentration in blood,8 and monitoring glucose levels in sweat is painless and stress-free. However, the requirements of accurate sweat-based glucose sensing are different from those of blood-based sensing. Therefore, an integrated system is needed that incorporates sensors and feedback-controlled transdermal drug delivery devices, to eliminate pain and stress and take into account factors that affect the accuracy of sensing.

Enzyme-based glucose sensors can be affected by environmental factors. For example, the mechanical deformation of wearable sensors during daily activities may lead to fractures in the sensor electronics that cause them to malfunction. The lactic acid present in sweat reduces the pH to 4–5, which affects the accuracy of enzyme-based sensors, as do variations in the ambient temperature. Therefore, a glucose monitoring system needs to be mechanically deformable, with correction of the results in real time based on simultaneous measurements of the pH and temperature. It would also be advantageous if the device were transparent, to make it discreet in use, and if microneedles were used for drug delivery, which would make the process painless.

Our recently developed graphene-based diabetes patch provides a potential solution to meet these needs (see Figure 1).9 The patch consists of multiple sensors, actuators, and sweat-control layers for the systematic collection of sweat, sensing of glucose, and feedback-controlled transdermal drug delivery. First, a layer for the uptake of sweat absorbs secreted sweat, of which the amount is monitored by an integrated humidity sensor. When the relative humidity exceeds 80%, other sensors (for example, glucose, pH, and temperature sensors) begin their measurements. The pH and temperature sensors measure the pH of sweat and the ambient temperature, respectively. These environmental parameters are used to correct the glucose concentration in sweat, which is measured by an integrated glucose sensor, in real time.


Figure 1. (a) Sweat control and sensing components of the diabetes patch (left) are integrated with the graphene hybrid electrode (right). (b) Photographs show the device on human skin (left) and when partially peeled off (right). Ag: Silver. AgCl: Silver chloride. Au: Gold. count. elect.: Counter-electrode. GP: Graphene. PANi: Polyaniline. PB: Prussian blue. PCM: Phase-change material. PEDOT: Polyethylenedioxythiophene. PVP: Polyvinylpyrrolidone.

Under normal conditions, microneedles in the patch are coated by the biocompatible phase-change material (PCM) tridecanoic acid and are separated from the interstitial fluid in the skin. These microneedles are made from the water-soluble polymer polyvinylpyrrolidone (PVP) and contain drugs active against type II diabetes, such as metformin. However, under hyperglycemic conditions, thermal actuation by embedded microheaters causes the PCM coating layer to melt at ∼41°C, which activates the microneedles. Consequently, the microneedles are dissolved by biological fluids, which enables transdermal drug delivery. We have demonstrated sensing using the diabetes patch on human skin, and successfully tested feedback-controlled drug delivery on genetically modified diabetic mice. In the case of hypoglycemia, an integrated strain gauge measures tremors and, when necessary, drug delivery is stopped accordingly.

To ensure that the electrochemical sensors are highly sensitive and mechanically soft, we use functionalized graphene synthesized by chemical vapor deposition (CVD). The graphene hybrid electrode, which consists of gold-doped graphene on a gold mesh, is not only highly transparent but also exhibits good electrical and electrochemical properties, for example, high conductivity.10 As it is mechanically soft, the graphene-based electrode can be used in wearable devices. Although graphene grown by CVD has good electrical, optical, and mechanical properties, its intrinsic electrochemical activity is low because of its low defect density. However, graphene hybrid structures functionalized with electrochemically active organic9 or inorganic10 materials display high sensitivity to biomarkers for use in electrochemical sensors.

These improvements to wearable diabetes patches provide non-invasive control of blood glucose levels via pain-free monitoring of blood glucose without blood sampling and feedback-controlled drug delivery without injections. These have both been important goals in the long-term treatment of diabetes. To improve the functioning of our devices, we now need to ensure the long-term reliability and stability of the glucose monitoring system and develop a more efficient method of sweat collection. Even while we are working on resolving these issues, our wearable electronic patches will still lead to a better future for diabetes patients.

This work was supported by IBS-R006-D1.


Dae-Hyeong Kim, Hyunjae Lee, Tae Kyu Choi
School of Chemical and Biological Engineering
Seoul National University
Seoul, Republic of Korea

Dae-Hyeong Kim is an associate professor in the School of Chemical and Biological Engineering. He has focused on stretchable electronics for biomedical and energy applications.

Hyunjae Lee is a PhD candidate in the School of Chemical and Biological Engineering, where he received his BS in 2010.

Tae Kyu Choi is an MS candidate in the School of Chemical and Biological Engineering. He received his BS in 2014 in the Department of Chemical Engineering at Pohang University of Science and Technology.


References:
1. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N. Engl. J. Med. 329, p. 977-986, 1993. doi:10.1056/NEJM199309303291401
2. D. Son, J. Lee, S. Qiao, R. Ghaffari, J. Kim, J. E. Lee, C. Song, et al., Multifunctional wearable devices for diagnosis and therapy of movement disorders, Nat. Nanotechnol. 9, p. 397-404, 2014. doi:10.1038/nnano.2014.38
3. J. Kim, M. Lee, H. J. Shim, R. Ghaffari, H. R. Cho, D. Son, Y. H. Jung, et al., Stretchable silicon nanoribbon electronics for skin prosthesis, Nat. Commun. 5, p. 5747, 2014. doi:10.1038/ncomms6747
4. M. K. Choi, J. Yang, K. Kang, D. C. Kim, C. Choi, C. Park, S. J. Kim, et al., Wearable red–green–blue quantum dot light-emitting diode array using high-resolution intaglio transfer printing, Nat. Commun. 6, p. 7149, 2015. doi:10.1038/ncomms8149
5. A. J. Bandodkar, W. Jia, C. Yard?mc?, X. Wang, J. Ramirez, J. Wang, Tattoo-based noninvasive glucose monitoring: a proof-of-concept study, Anal. Chem. 87, p. 394-398, 2015. doi:10.1021/ac504300n
6. W. Gao, S. Emaminejad, H. Y. Y. Nyein, S. Challa, K. Chen, A. Peck, H. M. Fahad, et al., Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis, Nature 529, p. 509-514, 2016. doi:10.1038/nature16521
7. D. P. Rose, M. E. Ratterman, D. K. Griffin, L. Hou, N. Kelley-Loughnane, R. R. Naik, J. A. Hagen, I. Papautsky, J. C. Heikenfeld, Adhesive RFID sensor patch for monitoring of sweat electrolytes, IEEE Trans. Biomed. Eng. 62, p. 1457-1465, 2014. doi:10.1109/TBME.2014.2369991
8. J. Moyer, D. Wilson, I. Finkelshtein, B. Wong, R. Potts, Correlation between sweat glucose and blood glucose in subjects with diabetes, Diabetes Technol. Ther. 14, p. 398-402, 2012. doi:10.1089/dia.2011.0262
9. H. Lee, T. K. Choi, Y. B. Lee, H. R. Cho, R. Ghaffari, L. Wang, H. J. Choi, et al., A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy, Nat. Nanotechnol. 11, p. 566-572,  2016. doi:10.1038/nnano.2016.38
10. H. Lee, Y. Lee, C. Song, H. R. Cho, R. Ghaffari, T. K. Choi, K. H. Kim, et al., An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment, Nat. Commun. 6, p. 10059, 2015. doi:10.1038/ncomms10059