Reduced Graphene Oxide Nanohybrid-Assembled Microneedles as Mini-Invasive Electrodes for Real-Time Transdermal Biosensing.

A variety of nanomaterial-based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real-time sensing in vivo. The application of microneedles (MN) may offer a solution for painless and minimally-invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H2 O2 electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water-soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO-integrated MNs for in situ and real-time sensing of H2 O2 in vivo are demonstrated both on pigskin and living mice. This work offers a unique real-time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally-invasive manner.

[1]  Abdulazeez T. Lawal.  Synthesis and utilisation of graphene for fabrication of electrochemical sensors. , 2015, Talanta.

[2]  Fenghua Zhang,et al.  Direct electrochemistry of cholesterol oxidase immobilized on chitosan–graphene and cholesterol sensing , 2015 .

[3]  Chia-Liang Sun,et al.  The simultaneous electrochemical detection of ascorbic acid, dopamine, and uric acid using graphene/size-selected Pt nanocomposites. , 2011, Biosensors & bioelectronics.

[4]  I. Palchetti,et al.  Self-powered microneedle-based biosensors for pain-free high-accuracy measurement of glycaemia in interstitial fluid. , 2015, Biosensors & bioelectronics.

[5]  Ryan F. Donnelly,et al.  Hydrogel-Forming Microneedles Prepared from “Super Swelling” Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery , 2014, PloS one.

[6]  Hayder A. Abdulbari,et al.  Electrochemical Biosensors: Electrode Development, Materials, Design, and Fabrication , 2017 .

[7]  Zhigang Zang,et al.  Enhanced performance of light-controlled conductive switching in hybrid cuprous oxide/reduced graphene oxide (Cu2O/rGO) nanocomposites. , 2017, Optics letters.

[8]  Seajin Oh,et al.  Analgesic Microneedle Patch for Neuropathic Pain Therapy. , 2017, ACS nano.

[9]  M. Vaezi,et al.  Exploring corrosion protection properties of solvent based epoxy-graphene oxide nanocomposite coatings on mild steel , 2017 .

[10]  S. Pervaiz,et al.  Intracellular superoxide and hydrogen peroxide concentrations: a critical balance that determines survival or death , 2001, Redox report : communications in free radical research.

[11]  Somasekhar R Chinnadayyala,et al.  Nonenzymatic determination of glucose at near neutral pH values based on the use of nafion and platinum black coated microneedle electrode array , 2018, Microchimica Acta.

[12]  Jules L. Hammond,et al.  Electrochemical biosensors and nanobiosensors , 2016, Essays in biochemistry.

[13]  Hui Jiang,et al.  Highly sensitive graphene-Pt nanocomposites amperometric biosensor and its application in living cell H2O2 detection. , 2014, Analytical chemistry.

[14]  Mark G. Allen,et al.  A patch type non-enzymatic biosensor based on 3D SUS micro-needle electrode array for minimally invasive continuous glucose monitoring , 2016 .

[15]  Xiaolian Sun,et al.  Dumbbell-like PtPd-Fe₃O₄ nanoparticles for enhanced electrochemical detection of H₂O₂. , 2012, Nano letters.

[16]  S. Varma,et al.  Hydrogen peroxide in human blood. , 1991, Free radical research communications.

[17]  Yueming Li,et al.  Preparation and electrochemical performance for methanol oxidation of pt/graphene nanocomposites , 2009 .

[18]  Paolo Bollella,et al.  Microneedle-based biosensor for minimally-invasive lactate detection. , 2019, Biosensors & bioelectronics.

[19]  Xiue Jiang,et al.  A facile one-pot synthesis of copper sulfide-decorated reduced graphene oxide composites for enhanced detecting of H2O2 in biological environments. , 2013, Analytical chemistry.

[20]  Jingyan Zhang,et al.  Graphene quantum dots/gold electrode and its application in living cell H2O2 detection. , 2013, Nanoscale.

[21]  Tianhui Xu,et al.  Simultaneous determination of dopamine and uric acid in the presence of ascorbic acid using Pt nanoparticles supported on reduced graphene oxide , 2014 .

[22]  Chao Gao,et al.  Ion Diffusion-Directed Assembly Approach to Ultrafast Coating of Graphene Oxide Thick Multilayers. , 2017, ACS nano.

[23]  K. Nahm,et al.  Conductive Polymer/Graphene Supported Platinum Nanoparticles as Anode Catalysts for the Extended Power Generation of Microbial Fuel Cells , 2014 .

[24]  Sanjiv Sharma,et al.  Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring , 2017, Sensing and Bio-Sensing Research.

[25]  Zhiwei Zhu,et al.  Biosensor based on ultrasmall MoS2 nanoparticles for electrochemical detection of H2O2 released by cells at the nanomolar level. , 2013, Analytical chemistry.

[26]  B. Liu,et al.  Touch-actuated microneedle array patch for closed-loop transdermal drug delivery , 2018, Drug delivery.

[27]  Mingce Long,et al.  One-step synthesis of Pt nanoparticles/reduced graphene oxide composite with enhanced electrochemical catalytic activity , 2013, Science China Chemistry.

[28]  Giuseppe Barillaro,et al.  Microneedles for Transdermal Biosensing: Current Picture and Future Direction , 2015, Advanced healthcare materials.

[29]  Wei Gao,et al.  Catalytic performance of Pt nanoparticles on reduced graphene oxide for methanol electro-oxidation , 2010 .

[30]  Mark R Prausnitz,et al.  Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin. , 2017, Annual review of chemical and biomolecular engineering.

[31]  Robert Langer,et al.  Microneedles for drug delivery via the gastrointestinal tract. , 2015, Journal of pharmaceutical sciences.

[32]  Abdullah M. Asiri,et al.  Cobalt nitride nanowire array as an efficient electrochemical sensor for glucose and H2O2 detection , 2018 .

[33]  Shifeng Hou,et al.  Graphene-supported platinum and platinum–ruthenium nanoparticles with high electrocatalytic activity for methanol and ethanol oxidation , 2010 .

[34]  Ronen Polsky,et al.  Integrated carbon fiber electrodes within hollow polymer microneedles for transdermal electrochemical sensing. , 2011, Biomicrofluidics.

[35]  Hye Rim Cho,et al.  Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module , 2017, Science Advances.

[36]  B. Halliwell,et al.  Hydrogen peroxide in the human body , 2000, FEBS letters.

[37]  P. Pelicci,et al.  Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? , 2007, Nature Reviews Molecular Cell Biology.

[38]  Fernando Soto,et al.  A microneedle biosensor for minimally-invasive transdermal detection of nerve agents. , 2017, The Analyst.

[39]  Victor J. Cadarso,et al.  Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes , 2016, Scientific Reports.

[40]  Congming Li,et al.  Graphene blended with SnO2 and Pd-Pt nanocages for sensitive non-enzymatic electrochemical detection of H2O2 released from living cells. , 2018, Analytica chimica acta.