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Graphene patch for Diabetes Management – A Medical Contribution of Nanotechnology

As scientists continue their research on combating Diabetes, biotechnology is progressing as well. A relatively new concept that is garnering excitement is a graphene patch with sensors, similar to a nicotine patch, that people can wear to measure glucose levels in perspiration. These glucose levels are similar to those in blood. Once measuring is complete, the graphene patch proceeds to administer the proper dose of an anti-diabetic drug through microscopic needles. This is an innovative therapy to handle diabetes and its consequences.

“Diabetes mellitus, commonly referred to as diabetes, is a big threat to human health globally. It is a disease characterized by high blood glucose levels (BGLs), which can cause severe damage to the eyes, kidneys, and nerves. In addition, it can also cause heart disease, strokes and even the need to remove limbs. Such complications can, however, be alleviated if controlled duly and effectively. Metabolites such as glucose are important indicators in diabetes management. The existing standard therapy for patients with insulin-dependent diabetes (type 1) and advanced patients with non-insulin-dependent diabetes (type 2) diabetics includes every day insulin injections, and frequent fingerstick calibrations to monitor BGLs. Frequent injections and fingerstick calibrations are painful and have a high risk of infection as a result of exposure to the environment and the low immunity of diabetics, hence a more accurate, riskless and less painful method is highly desirable. Therefore, intense scholarly interest has been aroused concerning the detection, tracking, and control of metabolites using optical, electromagnetic or electrochemical sensors.”1  

Integrated Glucose Monitoring and Diabetes Therapy System

 

Schematic diagram of the integrated glucose monitoring and diabetes therapy system
Schematic diagram of the integrated glucose monitoring and diabetes therapy system. (2)

 

“As sweat accumulates in the patch, the glucose it contains is monitored electrochemically on a graphene hybrid platform that also supports an array of other sensors (pH, humidity, mechanical strain). In response to the detected glucose, the actuation of thermoresponsive polymeric microneedles is initiated, releasing an appropriate quantity of diabetes medication. The graphene hybrid device connects electrically to a portable electrochemical analyzer, which acts as a power supply and controller that wirelessly transmits data to a remote mobile device (such as a smartphone).”3  

Scientists have cited the immediate rewards of this innovative approach to the management of Diabetes Mellitus, saying it is an ideal method due to the inconveniences of traditional invasive methods to administer medications, such as needles.

 

Smart patch for diabetes
Smart patch for diabetes. Wong, S. NewScientist. 2016. (4)

 

How Does It Work?

The device utilizes several sheets of a synthetic fluoropolymer called Nafion to absorb sweat. Then, the built-in sensors read the glucose levels accordingly. The graphene patch is made with electrochemical materials (by doping the graphene with gold atoms) that provide the device functionality to detect glucose.

The chemical reaction that occurs within the glucose sensors is prominent: Glucose oxidase is an enzyme that interacts with the glucose absorbed from sweat, resulting in hydrogen peroxide, which then pulls electrical current from the gold atom imbibed graphene. This electrical response corresponds to the quantity of surrounding glucose.

Using Sweat as a Diagnostic Tool

“Sweat is one of the most accessible body fluids, where its primary biological role is for thermoregulation. Conveniently, for sampling purposes, eccrine glands that excrete sweat can be found all over the body, where they are particularly concentrated in multiple locations, for example in the hands, feet, lower back and underarm. Sweat has been exploited for diagnostic purposes, in particular for the detection of disease markers such as sodium, potassium, calcium, phosphate, and glucose. It is also known that small-molecule drugs and their metabolites are present in sweat, thereby allowing the evaluation of drug efficacy. Sweat can be continuously accessed and its production can be stimulated on-demand at certain locations, for example by iontophoresis. By placing sensors in close contact with the skin, sweat samples can be processed rapidly without contamination. For many years, sweat has been used as a sampling medium of interest in sensing devices for confirming diseases, such as cystic fibrosis and for gaining other valuable information, relating to electrolyte balance, diet, injury, stress, medications, and hydration. The hydration status of individuals has become a relatively new area of interest for monitoring human performance, resulting in an increase in wearable smart devices on the global market. Most analytes contained in sweat tend to vary significantly between basal and exercising states, as well as between individuals. The reported glucose level in sweat for healthy patients is between 0.06 and 0.11 mM and between 0.01 and 1 mM for diabetics. The fluctuations in analyte concentrations result in a broad pH range of sweat, typically between pH 4.0–6.8 during exercise, which can impact on the effectiveness of chemical-sensing or biosensing techniques chosen for disease diagnosis or monitoring.”5 

The Functioning of Graphene Nano-Sensors

Another built-in attribute of this device is the versatility of the aforementioned sensors. They can read glucose presence in sweat and they also minimize possible measure reading errors by detecting pH and temperature levels. When the participants enlisted in the study wore this new device, the specialists found that the readings it gave before and after meals were the same as glucose meters available commercially.

“The gold studs were added in order to be able to read the glucose levels. The material can also be employed for the fabrication of wearable patches for diabetes monitoring and feedback therapy. The fabricated stretchable device structures a serpentine bilayer of gold mesh and gold doped graphene and forming an efficient electrochemical interface for the stable transfer of electrical signals. The fabricated patch mainly consisted of a heater, temperature, humidity, glucose, and pH sensors along with polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. An interesting fact of the fabricated is that the patch uses sweat to determine ‘sweat glucose’, which can be used to figure out blood glucose levels. They have used Metformin as an antidiabetic drug and showed that the patch can be thermally actuated to deliver Metformin and eventually can reduce the blood glucose levels in diabetic mice. These types of advances using nanomaterials and devices will provide some new opportunities for the treatment of chronic diseases like diabetes mellitus.”6

Demonstration of the wearable diabetes monitoring and therapy system in vivo

 

Demonstration of the wearable diabetes monitoring and therapy system in vivo
“(A) Optical image of the integrated wearable diabetes monitoring and therapy system connected to a portable electrochemical analyzer. The electrochemical analyzer wirelessly communicates with external devices via Bluetooth. (B) Optical image of the GP-hybrid electrochemical device array on the human skin with perspiration.”7

 

On the monitoring side of the patch, the sensors send the incoming signals for analysis, where analyzed information is then sent to a modern phone by wireless means.

“The detection of hyperglycemia — through the glucose and pH sensors — is the cue to actuate drug delivery from the device. The polymeric microneedles, which contain metformin (a drug commonly used in the treatment of type 2 diabetes), are coated with a hydrophobic layer of tridecanoic acid. This layer protects the microneedles from moisture when inserted into the skin and prevents the premature release of the metformin. When an elevated glucose level is detected, the heater embedded in the patch is triggered, warming the microneedles.”8 

The drug-dispensing system consists of sophisticated 1-mm-long fluoropolymer needles imbibed with metformin (an anti-diabetes medication) that puncture the epidermis and disintegrate to deliver this drug. Additionally, the needles have a coating of tridecylic acid. A mesh of gold graphene atop the needles heats up, and subsequently melts this coating. The melted acid then disintegrates into the dermis and delivers the intended drug with it. 

“Graphene biochemical sensors with solid-state Ag/AgCl counter electrodes show enhanced electrochemical activity, sensitivity, and selectivity in detecting important biomarkers contained in human sweat. The GP-hybrid (graphene-hybrid) interconnections and physical sensors efficiently transmit the signal through the stretchable array and supplement electrochemical sensors, respectively. The orchestrated monitoring of biomarkers and physiological cues with sweat control and transcutaneous drug delivery achieves a closed-loop, point-of-care treatment for diabetes. The detection of RH (relative humidity) over a critical point due to sweat activates the glucose sensing, which is corrected by simultaneous measurement of pH and temperature. High glucose concentration recordings trigger the embedded heaters to dissolve PCM (phase-change material) and as a result, bioresorbable microneedles release Metformin as a feedback transdermal drug delivery to the glucose sensing. The use of intrinsically soft materials enhances the conformal integration of devices with the human skin and thus improves the effectiveness of biochemical sensors and drug delivery. The wireless connectivity further highlights the practical applicability of the current patch system. These advances using nanomaterials and devices provide new opportunities for the treatment of chronic diseases such as diabetes mellitus.”9 

Conceptually, this new device is causing excitement. The scientific community is constantly making more vanguard attempts at improving life with Diabetes.

 

References:

(1) Conducting Polymers and Their Applications in Diabetes Management. Zhao, Y., Cao, L., Li, L., Cheng, W., Xu, L., Ping, X., Pan, L. & Shi, Y. Sensors. 2016. https://www.mdpi.com/1424-8220/16/11/1787/htm 

(2, 3, 8) Managing diabetes through the skin. Richard Guy. Nature Nanotechnology. 2016. https://www.nature.com/articles/nnano.2016.53 

(4) Smart patch for diabetes. Wong, S. NewScientist. 2016. https://www.newscientist.com/article/mg22930661-900-smart-patch-for-diabetes/

(5) Glucose Sensing for Diabetes Monitoring: Recent Developments. Bruen, D., Delaney, C., Florea, L. & Diamond, D. Sensors. 2017. https://www.mdpi.com/1424-8220/17/8/1866/htm 

(6, 7) Stimuli-responsive polymers for treatment of diabetes mellitus. Patra, S., Madhuri, R. & Sharma, P.K.  Advanced Nanocarrieres for Therapeutics. Volume 2. 2019. pg. 516, 518. https://books.google.co.ve/books?id=KOZ0DwAAQBAJ&pg=PA491&lpg=PA491&dq=Stimuli-responsive+polymers+for+treatment+of+diabetes+mellitus&source=bl&ots=PHkrUcuf9o&sig=ACfU3U02b-TplGQL3jcNMq2LRK9yHbPHWA&hl=es&sa=X&ved=2ahUKEwjvx9Lt5v3hAhWFm1kKHe2_BaQQ6AEwBHoECAkQAQ#v=onepage&q=Stimuli-responsive%20polymers%20for%20treatment%20of%20diabetes%20mellitus&f=false

(9) A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Lee, H., Kyu Choi, T., Bum Lee, Y., Rim Cho, H., Ghaffari, R., Wang, L ., Jin Choi, H., Dong Chung, T., Lu, N., Hyeon,  T., Hong Choi, S. & Kim, D-H. Nature Nanotechnology. 2016. https://www.nature.com/articles/nnano.2016.38 

 

María Laura Márquez
13 October, 2018

Written by

María Laura Márquez, general doctor graduated from The University of Oriente in 2018, Venezuela. My interests in the world of medicine and science, are focused on surgery and its breakthroughs. Nowadays I practice my profession...read more:

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