Diabetes is a chronic condition where the patient is unable to regulate their own blood glucose levels (1). Insulin is a peptide hormone produced by pancreatic islets beta cells: it breaks down glucose into glycogen that is absorbed by cells in the liver, fat and muscles. If blood glucose levels are not managed properly, it can result in patients developing life-threatening complications like diabetic ketoacidosis (DKA), heart attack or stroke.
In 2021, it was estimated around 537 million adults between the ages of 20-79 years old were living with diabetes: this is expected to rise to 643 million by 2030. 1 in 2 adults (240 million) with diabetes went undiagnosed and 541 million adults had an increased risk of developing type 2 diabetes (2).
There are 3 main types of Diabetes:
|Type 1 Diabetes||The inability to produce insulin cells due to the body's own immune system attacking and destroying the cells that produce insulin. This results in no/reduce insulin produced to trigger cells to break down glucose and regulate blood glucose levels||Is an autoimmune disease that can occur very quickly with no specific trigger.|
|Type 2 Diabetes||Insulin receptor cells gradually lose their sensitivity and become resistant to insulin causing a reduction in cell response to break down glucose in the blood to regulate blood glucose levels, resulting in high glucose levels||Developed over a long period of time. Often linked with overweight, lack of physical activity or family history|
|Gestational Diabetes||An insufficient amount of insulin is produced to meet the extra requirements during pregnancy. This means that excess glucose will remain in the blood causing high blood glucose levels||Some women develop this during pregnancy, more commonly in the 2nd and 3rd trimesters. Usually disappears after giving birth|
Figure 1: Types of diabetes and their onset (Adapted from reference 3)
Significant research has gone into glucose monitoring and many diagnostic devices are commercially available on the market to monitor glucose levels in the body including the classic finger-prick method and invasive continuous monitoring systems (CGMs), integrating electrochemical biosensors, especially for point-of-care diagnostics (4). However, biosensors use enzymes such as glucose oxidase for detection. Although enzymes are useful for single-point and short-term CGM sensors, they are easily affected by environmental factors including pH and temperature and are dependent on localised oxygen concentration in the analyte. Hence, incorporation of enzymes into the ‘next generation’ of glucose sensors is challenging as these sensors are replaced on a 90+ day basis, around ten times longer than the current enzyme based CGM systems are expected to last. An enzyme-free glucose monitoring sensor could address the issue of longevity for the next generation of diagnostics.
Integrated Graphene's CSO Marco Caffio and Pablo Lozano Sanchez worked alongside Professor Tony James, Simon Wikeley, Steven Bull, Philip Fletcher and Frank Marken at the University of Bath to develop a novel electrochemical glucose chemo-sensing assay based on boronic acid and graphene foam: the technique is low-cost and effective for reporting glucose concentrations.
Research has gone into the use of boronic acids for glucose sensing due to their ability to form reversible complexes with sugars, carbohydrates and more. However, most research is in fluorescent or optical detection. Boronic acids have been developed for the electrochemical detection and analysis of other analytes.
Figure 2: Glucose breaks apart the polymer and receptor layers, enabling electrochemical detection (Simon, Tony and Frank from the University of Bath)
Graphene is the substrate platform that boronic acid is adsorbed onto. A layer of redox-active polymer, poly-nordihydroguaiaretic acid (poly-NHG) is bound to boronic acid: this was incorporated into the assay design as boronic acid and glucose are not redox-active materials.
The sensor works based on polymer displacement whereby the polymer and glucose molecules compete for a limited number of boronic acid binding sites. In a concentrated glucose environment, the polymer loses its adherence to boronic acid, creating an electrochemical shift which detected to generate a measurable output. As the current produced is proportional to the amount of displaced polymer, this allows for an accurate recording of glucose concentration in the sample.
Unlike current glucose sensing electrochemical biosensors on the market that use enzymes, this sensor is less prone to environmental factors: this is due to the assay using chemicals rather than biological components. The polymer used takes on additional functions to preserve the assay and filter out larger molecules which may interrupt with the glucose sensing mechanism. The assay also displays a wider range of glucose concentrations above and below the current commercialised biosensors range.
This breakthrough gives rise to a future of enzyme-free glucose monitoring sensors that can relieve some of the socio-economical burdens that diabetes is presenting. More accurate, non-invasive glucose monitoring techniques are desirable from a practical and healthcare standpoint; better blood glucose control in diabetic patients reduces the incidence of long-term complications, alleviating the burden on healthcare systems. Although the technology still needs to be optimised and real or simulated long-term monitoring needs to be investigated, the proof of concept for the next generation is exciting and has great potential.
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- Menon S, Mathew MR, Sam S, Keerthi K, Kumar KG. Recent advances and challenges in electrochemical biosensors for emerging and re-emerging infectious diseases. J Electroanal Chem (Lausanne). 2020 Dec 1;878:114596. doi: 10.1016/j.jelechem.2020.114596. Epub 2020 Aug 25. PMID: 32863810; PMCID: PMC7446658.
- Lacina K, Skládal P, James TD. Boronic acids for sensing and other applications - a mini-review of papers published in 2013. Chem Cent J. 2014;8(1):60. Published 2014 Oct 18. doi:10.1186/s13065-014-0060-5