Microporous Nanocomposite Enabled Microfluidic Biochip for Cardiac Biomarker Detection.

This paper demonstrates an ultrasensitive microfluidic biochip nanoengineered with microporous manganese-reduced graphene oxide nanocomposite for detection of cardiac biomarker, namely human cardiac troponin I. In this device, the troponin sensitive microfluidic electrode consisted of a thin layer of manganese-reduced graphene oxide (Mn3O4-RGO) nanocomposite material. This nanocomposite thin layer was formed on surface of a patterned indium tin oxide substrate after modification with 3-aminopropyletriethoxysilane and was assembled with a polydimethylsiloxane-based microfluidic system. The nanoengineered microelectrode was functionalized with antibodies specific to cardiac troponin I. The uniformly distributed flower-shaped nanostructured manganese oxide (nMn3O4) onto RGO nanosheets offered large surface area for enhanced loading of antibody molecules and improved electrochemical reaction at the sensor surface. This microfluidic device showed an excellent sensitivity of log [87.58] kΩ/(ng mL-1)/cm2 for quantification of human cardiac troponin I (cTnI) molecules in a wide detection range of 0.008-20 ng/mL. This device was found to have high stability, high reproducibility, and minimal interference with other biomarkers cardiac troponin C and T, myoglobin, and B-type natriuretic peptide. These advantageous features of the Mn3O4-RGO nanocomposite, in conjunction with microfluidic integration, enabled a promising microfluidic biochip platform for point-of-care detection of cardiac troponin.

[1]  X. Lou,et al.  Facile synthesis of metal oxide/reduced graphene oxide hybrids with high lithium storage capacity and stable cyclability. , 2011, Nanoscale.

[2]  J Wang,et al.  Electrochemical enzyme immunoassays on microchip platforms. , 2001, Analytical chemistry.

[3]  R. Li,et al.  Controlled synthesis of Zirconium Oxide on graphene nanosheets by atomic layer deposition and its growth mechanism , 2013 .

[4]  J. Greer,et al.  Ultrahigh sensitivity assays for human cardiac troponin I using TiO2 nanotube arrays. , 2012, Lab on a chip.

[5]  W. Lu,et al.  Improved synthesis of graphene oxide. , 2010, ACS nano.

[6]  J. Pinto,et al.  Composite structure and properties of Mn3O4/graphene oxide and Mn3O4/graphene , 2013 .

[7]  Kun Wang,et al.  TiO2-decorated graphene nanohybrids for fabricating an amperometric acetylcholinesterase biosensor. , 2011, The Analyst.

[8]  G. Urban,et al.  Polymer-modified microfluidic immunochip for enhanced electrochemical detection of troponin I , 2015 .

[9]  Akihiko Hirata,et al.  Nanoporous metal/oxide hybrid electrodes for electrochemical supercapacitors. , 2011, Nature nanotechnology.

[10]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[11]  Jeong-Woo Choi,et al.  A glucose biosensor based on TiO2-Graphene composite. , 2012, Biosensors & bioelectronics.

[12]  Xue-wei Cao,et al.  Vibrational properties of graphene and graphene layers , 2009 .

[13]  Kai Yang,et al.  Nano-Graphene in Biomedicine: Theranostic Applications , 2013 .

[14]  Kyusik Yun,et al.  Graphene oxide-modified ZnO particles: synthesis, characterization, and antibacterial properties , 2015, International journal of nanomedicine.

[15]  R. John,et al.  In-situ electrosynthesized nanostructured Mn3O4-polyaniline nanofibers- biointerface for endocrine disrupting chemical detection , 2016 .

[16]  Xiaodong Wu,et al.  Graphene oxide--MnO2 nanocomposites for supercapacitors. , 2010, ACS nano.

[17]  Li Zhang,et al.  Transition metal oxide and graphene nanocomposites for high-performance electrochemical capacitors. , 2012, Physical chemistry chemical physics : PCCP.

[18]  Lin Xu,et al.  Synthesis of graphene oxide based CuO nanoparticles composite electrode for highly enhanced nonenzymatic glucose detection. , 2013, ACS applied materials & interfaces.

[19]  S. Shanmugam,et al.  Polyoxometalate-reduced graphene oxide hybrid catalyst: synthesis, structure, and electrochemical properties. , 2013, ACS applied materials & interfaces.

[20]  D. Beebe,et al.  The present and future role of microfluidics in biomedical research , 2014, Nature.

[21]  S. Dong,et al.  Electrochemical sensing and biosensing platform based on chemically reduced graphene oxide. , 2009, Analytical chemistry.

[22]  M. Meyyappan,et al.  Label-free detection of cardiac troponin-I using carbon nanofiber based nanoelectrode arrays. , 2013, Analytical chemistry.

[23]  P. Kamat Graphene‐Based Nanoarchitectures. Anchoring Semiconductor and Metal Nanoparticles on a Two‐Dimensional Carbon Support , 2010 .

[24]  Junhong Chen,et al.  Ultrasensitive chemical sensing through facile tuning defects and functional groups in reduced graphene oxide. , 2014, Analytical chemistry.

[25]  S. Stankovich,et al.  Graphene-based composite materials , 2006, Nature.

[26]  S. Yadav,et al.  Pearl shaped highly sensitive Mn3O4 nanocomposite interface for biosensor applications. , 2014, Biosensors & bioelectronics.

[27]  Mario Plebani,et al.  Recommendations for the use of cardiac troponin measurement in acute cardiac care. , 2010, European heart journal.

[28]  P. Kamat,et al.  TiO2-graphene nanocomposites. UV-assisted photocatalytic reduction of graphene oxide. , 2008, ACS nano.

[29]  Keyur K. Gandhi,et al.  Solution processed reduced graphene oxide/metal oxide hybrid electron transport layers for highly efficient polymer solar cells , 2013 .

[30]  Roberta Bussamara,et al.  Controlled synthesis of Mn3O4 nanoparticles in ionic liquids. , 2013, Dalton transactions.

[31]  Dongxue Han,et al.  Reinforcement of silica with single-walled carbon nanotubes through covalent functionalization , 2006 .

[32]  B. D. Malhotra,et al.  Mesoporous Few-Layer Graphene Platform for Affinity Biosensing Application. , 2016, ACS applied materials & interfaces.

[33]  J. Yue,et al.  General synthesis of hollow MnO2, Mn3O4 and MnO nanospheres as superior anode materials for lithium ion batteries , 2014 .

[34]  Md Azahar Ali,et al.  Self assembled DC sputtered nanostructured rutile TiO₂ platform for bisphenol A detection. , 2015, Biosensors & bioelectronics.

[35]  Xuefeng Guo,et al.  Carbon nanomaterials field-effect-transistor-based biosensors , 2012 .

[36]  Alessandra Bonanni,et al.  Graphene for electrochemical sensing and biosensing , 2010 .

[37]  Minghong Wu,et al.  Facile synthesis of three-dimensional Mn3O4 hierarchical microstructures and their application in the degradation of methylene blue , 2015 .

[38]  Xiaoyun Bai,et al.  Electrochemical biosensor based on reduced graphene oxide modified electrode with Prussian blue and poly(toluidine blue O) coating , 2013 .

[39]  Ashutosh Sharma,et al.  Self-organized macroporous thin carbon films for supported metal catalysis , 2013 .

[40]  M. Meyyappan,et al.  Silicon nanowire biosensors for detection of cardiac troponin I (cTnI) with high sensitivity. , 2016, Biosensors & bioelectronics.

[41]  Huafeng Yang,et al.  Covalent functionalization of chemically converted graphene sheets via silane and its reinforcement , 2009 .

[42]  Kai Yang,et al.  Nano-graphene in biomedicine: theranostic applications. , 2013, Chemical Society reviews.

[43]  Alberto Escarpa,et al.  Carbon nanotubes press-transferred on PMMA substrates as exclusive transducers for electrochemical microfluidic sensing. , 2012, Analytical chemistry.

[44]  Abdul Rahman Mohamed,et al.  Multi-walled carbon nanotubes modified with (3-aminopropyl)triethoxysilane for effective carbon dioxide adsorption , 2013 .

[45]  S W Sharkey,et al.  Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I. , 1997, Clinical chemistry.

[46]  Md. Azahar Ali,et al.  In situ integration of graphene foam-titanium nitride based bio-scaffolds and microfluidic structures for soil nutrient sensors. , 2017, Lab on a chip.

[47]  Wei Gao,et al.  New insights into the structure and reduction of graphite oxide. , 2009, Nature chemistry.

[48]  Junhua Wei,et al.  A reduced graphene oxide based electrochemical biosensor for tyrosine detection. , 2012, Nanotechnology.

[49]  Saurabh Srivastava,et al.  Electrophoretically deposited reduced graphene oxide platform for food toxin detection. , 2013, Nanoscale.