Ultrasensitive, Label Free, Chemiresistive Nanobiosensor Using Multiwalled Carbon Nanotubes Embedded Electrospun SU-8 Nanofibers

This paper reports the synthesis and fabrication of aligned electrospun nanofibers derived out of multiwalled carbon nanotubes (MWCNTs) embedded SU-8 photoresist, which are targeted towards ultrasensitive biosensor applications. The ultrasensitivity (detection in the range of fg/mL) and the specificity of these biosensors were achieved by complementing the inherent advantages of MWCNTs such as high surface to volume ratio and excellent electrical and transduction properties with the ease of surface functionalization of SU-8. The electrospinning process was optimized to precisely align nanofibers in between two electrodes of a copper microelectrode array. MWCNTs not only enhance the conductivity of SU-8 nanofibers but also act as transduction elements. In this paper, MWCNTs were embedded way beyond the percolation threshold and the optimum percentage loading of MWCNTs for maximizing the conductivity of nanofibers was figured out experimentally. As a proof of concept, the detection of myoglobin, an important biomarker for on-set of Acute Myocardial Infection (AMI) has been demonstrated by functionalizing the nanofibers with anti-myoglobin antibodies and carrying out detection using a chemiresistive method. This simple and robust device yielded a detection limit of 6 fg/mL.

[1]  Fangqiong Tang,et al.  A novel platform for enhanced biosensing based on the synergy effects of electrospun polymer nanofibers and graphene oxides. , 2013, The Analyst.

[2]  Raj Mutharasan,et al.  Piezoelectric-excited millimeter-sized cantilever (PEMC) sensors detect Bacillus anthracis at 300 spores/mL. , 2006, Biosensors & bioelectronics.

[3]  L. Hood,et al.  Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood , 2008, Nature Biotechnology.

[4]  J. Fritz Cantilever biosensors. , 2008, The Analyst.

[5]  Anja Boisen,et al.  SU-8 Cantilevers for Bio/chemical Sensing; Fabrication, Characterisation and Development of Novel Read-out Methods , 2008, Sensors.

[6]  R. Muller,et al.  SU-8 micro-biosensor based on Mach-Zehnder interferometer , 2005 .

[7]  V. Rao,et al.  Polymer microcantilever biochemical sensors with integrated polymer composites for electrical detection , 2009 .

[8]  D. Janes,et al.  Co‐Percolating Graphene‐Wrapped Silver Nanowire Network for High Performance, Highly Stable, Transparent Conducting Electrodes , 2013 .

[9]  Hao Jiang,et al.  Bimaterial Microcantilevers as a Hybrid Sensing Platform , 2008 .

[10]  N. Allbritton,et al.  Surface graft polymerization of SU-8 for bio-MEMS applications , 2007 .

[11]  Mark A. Billadeau,et al.  Carbon Nanotube‐Based Biosensor , 2003 .

[12]  Yuejun Kang,et al.  Protein covalently conjugated SU-8 surface for the enhancement of mesenchymal stem cell adhesion and proliferation. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[13]  J. Niazi,et al.  Biosensors for cardiac biomarkers detection: A review , 2012 .

[14]  Yuehe Lin,et al.  Glucose Biosensors Based on Carbon Nanotube Nanoelectrode Ensembles , 2004 .

[15]  Wei Wang,et al.  PDMS gold nanoparticle composite film-based silver enhanced colorimetric detection of cardiac troponin I , 2010 .

[16]  O. I. Kalaoglu-Altan,et al.  "Clickable" Polymeric Nanofibers through Hydrophilic-Hydrophobic Balance: Fabrication of Robust Biomolecular Immobilization Platforms. , 2015, Biomacromolecules.

[17]  Xianfeng Zhang,et al.  Iminodiacetic acid-functionalized gold nanoparticles for optical sensing of myoglobin via Cu2+ coordination. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[18]  Xinhua Xu,et al.  ELECTROSPUN POLY (VINYL ALCOHOL)/GLUCOSE OXIDASE BIOCOMPOSITE MEMBRANES FOR BIOSENSOR APPLICATIONS , 2006 .

[19]  A. Gopalan,et al.  Electrospun poly(vinylidene fluoride)/poly(aminophenylboronic acid) composite nanofibrous membrane as a novel glucose sensor. , 2007, Analytical biochemistry.

[20]  Ashok Mulchandani,et al.  Carbon nanotubes-based chemiresistive biosensors for detection of microorganisms. , 2010, Biosensors & bioelectronics.

[21]  Vincent M. Rotello,et al.  Enzyme-amplified array sensing of proteins in solution and in biofluids. , 2010, Journal of the American Chemical Society.

[22]  Kemin Wang,et al.  Sensitive point-of-care monitoring of cardiac biomarker myoglobin using aptamer and ubiquitous personal glucose meter. , 2015, Biosensors & bioelectronics.

[23]  V. V. Shumyantseva,et al.  Electrochemical immunoanalysis of cardiac myoglobin , 2010, Biomeditsinskaia khimiia.

[24]  Raj Mutharasan,et al.  PEMC-based method of measuring DNA hybridization at femtomolar concentration directly in human serum and in the presence of copious noncomplementary strands. , 2007, Analytical chemistry.

[25]  Ramanathan Nagarajan,et al.  Role of single-walled carbon nanotubes on ester hydrolysis and topography of electrospun bovine serum albumin/poly(vinyl alcohol) membranes. , 2014, ACS applied materials & interfaces.

[26]  S. Ramakrishna,et al.  Polymer Nanofibers for Biosensor Applications , 2007 .

[27]  B. D. Malhotra,et al.  Highly sensitive biofunctionalized mesoporous electrospun TiO(2) nanofiber based interface for biosensing. , 2014, ACS applied materials & interfaces.

[28]  Fabrication and electrical conductivity of suspended carbon nanofiber arrays , 2011 .

[29]  A. Morales,et al.  Electrical percolation, morphological and dispersion properties of MWCNT/PMMA nanocomposites , 2014 .

[30]  K. Sawicka,et al.  Electrospun biocomposite nanofibers for urea biosensing , 2005 .

[31]  Bin Ding,et al.  Electrospun nanomaterials for ultrasensitive sensors , 2010, Materials Today.

[32]  S. Mukherji,et al.  Simple surface modification techniques for immobilization of biomolecules on SU-8 , 2009, Journal of materials science. Materials in medicine.

[33]  S. Garimella,et al.  Nanotextured superhydrophobic electrodes enable detection of attomolar-scale DNA concentration within a droplet by non-faradaic impedance spectroscopy. , 2013, Lab on a chip.

[34]  V. Rao,et al.  Silanization and antibody immobilization on SU-8 , 2007 .

[35]  Sam S. Yoon,et al.  Novel composite layer based on electrospun polymer nanofibers for efficient light scattering. , 2015, ACS applied materials & interfaces.

[36]  Tina M. Battaglia,et al.  Quantitative measurement of cardiac markers in undiluted serum. , 2007, Analytical chemistry.

[37]  Dirk Herrmann,et al.  An Introduction To Electrospinning And Nanofibers , 2016 .

[38]  Charles M. Lieber,et al.  Direct ultrasensitive electrical detection of DNA and DNA sequence variations using nanowire nanosensors , 2004 .

[39]  Nicole Jaffrezic-Renault,et al.  One-Step Fabrication of Electrospun Photo-Cross-Linkable Polymer Nanofibers Incorporating Multiwall Carbon Nanotubes and Enzyme for Biosensing , 2015 .

[40]  S. Kundu,et al.  Electrospinning: a fascinating fiber fabrication technique. , 2010, Biotechnology advances.

[41]  Miguel Holgado,et al.  Label-free biosensing by means of periodic lattices of high aspect ratio SU-8 nano-pillars. , 2010, Biosensors & bioelectronics.

[42]  R. Puers,et al.  Diffusing and swelling in SU-8: insight in material properties and processing , 2010 .

[43]  David M. Rissin,et al.  Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations , 2010, Nature Biotechnology.

[44]  David Erickson,et al.  Nanobiosensors: optofluidic, electrical and mechanical approaches to biomolecular detection at the nanoscale , 2008, Microfluidics and nanofluidics.

[45]  T. Nishi,et al.  Dramatically improved dielectric properties of polymer composites by controlling the alignment of carbon nanotubes in matrix , 2014 .

[46]  A. Boisen,et al.  Cantilever-like micromechanical sensors , 2011 .

[47]  Jeong-O Lee,et al.  Single-walled carbon nanotube biosensors using aptamers as molecular recognition elements. , 2005, Journal of the American Chemical Society.

[48]  Soumyo Mukherji,et al.  A novel dry method for surface modification of SU-8 for immobilization of biomolecules in Bio-MEMS. , 2007, Biosensors & bioelectronics.

[49]  Anja Boisen,et al.  Polymeric cantilever-based biosensors with integrated readout , 2006 .

[50]  R. Subramanian,et al.  Fabrication of impedimetric sensors for label-free Point-of-Care immunoassay cardiac marker systems, with passive microfluidic delivery , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[51]  Yilun Luo,et al.  Novel Biosensor Based on Electrospun Nanofiber and Magnetic Nanoparticles for the Detection of E. coli O157:H7 , 2012, IEEE Transactions on Nanotechnology.

[52]  Suna Timur,et al.  Bioactive surface design based on functional composite electrospun nanofibers for biomolecule immobilization and biosensor applications. , 2014, ACS applied materials & interfaces.

[53]  Moon J. Kim,et al.  HIGHLY REPRODUCIBLE SINGLE POLYANILINE NANOWIRE USING ELECTROPHORESIS METHOD , 2008 .

[54]  Chang Liu,et al.  Comparison of electrical properties between multi-walled carbon nanotube and graphene nanosheet/high density polyethylene composites with a segregated network structure , 2011 .

[55]  Amine functionalized SU-8 layer guiding Love mode surface acoustic wave , 2010 .

[56]  Gerald Urban,et al.  Micro- and nanobiosensors—state of the art and trends , 2008 .

[57]  A. Mulchandani,et al.  Conducting polymer functionalized single-walled carbon nanotube based chemiresistive biosensor for the detection of human cardiac myoglobin , 2014 .

[58]  Chad A. Mirkin,et al.  Drivers of biodiagnostic development , 2009, Nature.

[59]  M. Yun,et al.  Detection of Cardiac Biomarkers Using Single Polyaniline Nanowire-Based Conductometric Biosensors , 2012, Biosensors.

[60]  C. M. Wu,et al.  Graphene modified electrospun poly(vinyl alcohol) nanofibrous membranes for glucose oxidase immobilization , 2014 .

[61]  Il-Hoon Cho,et al.  Chemiluminometric enzyme-linked immunosorbent assays (ELISA)-on-a-chip biosensor based on cross-flow chromatography. , 2009, Analytica chimica acta.

[62]  A. Mulchandani,et al.  Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease , 2014 .

[63]  Olivia Freeman,et al.  Talking points personal outcomes approach: practical guide. , 2012 .

[64]  Y. Huangb,et al.  UV-LIGA interferometer biosensor based on the SU-8 optical waveguide , 2005 .

[65]  Kenzo Maehashi,et al.  Label-free protein biosensor based on aptamer-modified carbon nanotube field-effect transistors. , 2007, Analytical chemistry.

[66]  Jin-Woo Choi,et al.  Conducting Polyaniline Nanowire and Its Applications in Chemiresistive Sensing , 2013, Nanomaterials.

[67]  H. Hill,et al.  The flow cytometric analysis of cytokines using multi-analyte fluorescence microarray technology. , 2006, Methods.

[68]  T. Desai,et al.  Surface modification of SU-8 for enhanced biofunctionality and nonfouling properties. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[69]  Zhiqiang Su,et al.  Electrospinning: a facile technique for fabricating polymeric nanofibers doped with carbon nanotubes and metallic nanoparticles for sensor applications , 2014 .

[70]  D. Chan,et al.  Immunoassay : a practical guide , 1987 .

[71]  L M Lechuga,et al.  Highly sensitive polymer-based cantilever-sensors for DNA detection. , 2005, Ultramicroscopy.

[72]  Jianbo Jia,et al.  Nonenzymatic glucose sensor based on graphene oxide and electrospun NiO nanofibers , 2012 .