High-Performance Intraocular Biosensors from Chitosan-Functionalized Nitrogen-Containing Graphene for the Detection of Glucose

Abstract

The noninvasive and real-time detection of glucose sugar from tears is promising for the early diagnosis and treatment of chronic diseases such as diabetes. However, its realization is a big challenge. A suitable biosensor electrode that can closely fit the eye and be electrochemically sensitive is still unrealized. In this work, nitrogen-doped graphene (N-G) was used as an ophthalmic electrode in a high-performance intraocular biosensor. The use of N-G has been reported elsewhere before as it is highly electroactive and so has a particular use in biosensors. We hereby present a novel procedure for making carboxylated chitosan-functionalized nitrogen-containing graphene (GC–COOH) by using a one-step ball-milling process. This process does not use toxic chemicals, flammable gases, or a high temperature. It is thus particularly easy to perform. The fabricated nanomaterial had a high electroactivity and was easily assembled as a glucose biosensor by the immobilization of glucose oxidase. The thus constructed biosensor has a high sensitivity at 9.7 μA mM–1 cm–2, a broad linear range at 12 mM, and a good detection limit of 9.5 μM. It was able to maintain this activity after a month of storage. We also report the intraocular use of this constructed biosensor. The as-prepared GC–COOH was found to be highly biocompatible to ophthalmologic cells such as corneal epithelial and retinal pigment epithelium cells. No change in the intraocular pressure or the corneal structure was measured in a New Zealand white rabbit model. The as-assembled sensor was worn by the animals for more than 24 h without undue impact. This result confirmed the biosensor’s potential for intraocular application in the clinic. Its assembly into a useful sensor shown here has great potential to provide real-time monitoring of glucose levels in tear fluids of patients with high sugar levels.

A novel Vancomycin‐Functionalized‐Magnetic Graphene Composite for Use as a Near‐Infrared‐Induced Synergistic Chemo‐Photothermal Antibacterial

“…The formation of the nitrogen‐containing graphene nanosheets was described in a previous study by the Authors. [ 25 ] During the ball‐milling process, nitrogen‐containing chitosan was initially functionalized on the edge of graphite sheets via a solid‐phase mechanochemical reaction. The continuously increased content of nitrogen‐containing chitosan helped to expand the layered space between graphite sheets, and facilitated the exfoliation of nanoscaled graphene sheets along with the milling shear‐force.…”

“…[ 24 ] Carboxylated chitosan was applied to prepare chitosan‐modified graphene (CG) via an edge‐functionalized ball milling method reported previously by the Author's group. [ 25 ] This composite helped to encapsulate bacteria in an acidic microenvironment. [ 26 ] The nitrogen‐containing content of the CG improved its photothermal properties.…”

Graphene Family Nanomaterials in Ocular Applications: Physicochemical Properties and Toxicity

“…In addition to contact lenses, recently, a high-performance intraocular biosensor made of carboxylated chitosan-functionalized nitrogen-containing graphene (GC-COOH) was fabricated for detection of glucose sugar from tears. 148 In general, it is crucially important for diabetic patients to detect their glucose sugar level for early treatment, so the noninvasive and real-time detection from tears will be very valuable. In this study, a high-performance intraocular biosensor containing nitrogen-doped graphene was developed, which showed a high electroactive property that can act as an ophthalmic electrode.…”

Advances and current challenges in non‐invasive wearable sensors and wearable biosensors—A mini‐review

“…In this context, Zou and co‐works (Zou et al, 2019) developed an intraocular biosensor made by Chitosan functionalized nitrogen/graphene for glucose detection. Due to the sp 2 ‐hybridization from graphene structures, it allows a reactive site for electrochemical reactions, and this reactivity is intensified when associated with nitrogen.…”