Label-free electronic detection of interleukin-6 using horizontally aligned carbon nanotubes

A facile, sensitive, and label-free assay for detection of interleukin-6 (IL-6) using liquid-gated field-effect transistor (FET) sensors based on horizontally aligned single-walled carbon nanotubes (SWCNT) is proposed. This approach relies on the drain current (Id) responses of the transistor upon interactions of IL-6 with its corresponding antibody (IL-6R) immobilized on SWCNT. The proposed immunosensor exhibits superior sensitivity (limit-of-detection = 1.37 pg/mL) in virtue of the reduced tube-to-tube contact resistance, good selectivity (no responses to bovine serum albumin and cysteine were observed and detection of target molecules in serum was achieved) as a result of the highly specific interaction between IL-6 and IL-6R, and excellent stability (no significant degradation in the electronic performance after storage under ambient conditions for up to 3 months) in virtue of the strong adhesion of CNT to the quartz substrate and good horizontal alignment of these tubes. Therefore, the proposed immunosensor is a promising platform for early diagnosis of various diseases (including some cancers) that can be indicated by the circulating level of IL-6.

[1]  T. Goswami,et al.  Carbon nanotubes – Production and industrial applications , 2007 .

[2]  Xu Hun,et al.  Functionalized fluorescent core-shell nanoparticles used as a fluorescent labels in fluoroimmunoassay for IL-6. , 2007, Biosensors & bioelectronics.

[3]  A. D. de Vos,et al.  Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera. , 1991, Journal of immunological methods.

[4]  M. Nimmo,et al.  The response of circulating levels of the interleukin-6/interleukin-6 receptor complex to exercise in young men. , 2009, Cytokine.

[5]  Luisa Torsi,et al.  A sensitivity-enhanced field-effect chiral sensor. , 2008, Nature materials.

[6]  John A. Rogers,et al.  Improved Synthesis of Aligned Arrays of Single-Walled Carbon Nanotubes and Their Implementation in Thin Film Type Transistors† , 2007 .

[7]  P. Heinrich,et al.  Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. , 1998, The Biochemical journal.

[8]  Chien-Ming Wu,et al.  Quantification of Interleukin-6 in cell culture medium using surface plasmon resonance biosensors. , 2010, Cytokine.

[9]  J. Simons,et al.  Interleukin-6: a candidate mediator of human prostate cancer morbidity. , 1995, Urology.

[10]  H. Dai,et al.  Noncovalent sidewall functionalization of single-walled carbon nanotubes for protein immobilization. , 2001, Journal of the American Chemical Society.

[11]  Kazuhiko Matsumoto,et al.  Protein Sensor Using Carbon Nanotube Field Effect Transistor , 2005 .

[12]  T. Hirano,et al.  Interleukin-6: possible implications in human diseases , 1989, La Ricerca in clinica e in laboratorio.

[13]  P. Lansdorp,et al.  Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[14]  I. Christie,et al.  Measurement of cytokines in sweat patches and plasma in healthy women: validation in a controlled study. , 2006, Journal of immunological methods.

[15]  Zhenan Bao,et al.  Sorted and aligned single-walled carbon nanotube networks for transistor-based aqueous chemical sensors. , 2009, ACS nano.

[16]  Qiyuan He,et al.  The mechanism of graphene oxide as a growth template for complete reduced graphene oxide coverage on an SiO2 substrate , 2014 .

[17]  M. Jourdan,et al.  Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. , 1989, Blood.

[18]  H. Okazaki,et al.  Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells: a potential mechanism of its anti-inflammatory action. , 1995, Biochemical and biophysical research communications.

[19]  D. MacPhee Methodological considerations for improving Western blot analysis. , 2010, Journal of pharmacological and toxicological methods.

[20]  Limin Huang,et al.  Long and oriented single-walled carbon nanotubes grown by ethanol chemical vapor deposition , 2004 .

[21]  B. Liedberg,et al.  Aligned carbon nanotubes on quartz substrate for liquid gated biosensing. , 2010, Biosensors & bioelectronics.

[22]  Minghui Yang,et al.  Electrochemical sensor utilizing ferrocene loaded porous polyelectrolyte nanoparticles as label for the detection of protein biomarker IL-6 , 2011 .

[23]  Peter Schjerling,et al.  Pro‐ and anti‐inflammatory cytokine balance in strenuous exercise in humans , 1999, The Journal of physiology.

[24]  Jian-Rong Zhang,et al.  A new signal amplification strategy of photoelectrochemical immunoassay for highly sensitive interleukin-6 detection based on TiO2/CdS/CdSe dual co-sensitized structure. , 2014, Biosensors & bioelectronics.

[25]  B. Pedersen,et al.  Evidence that interleukin‐6 is produced in human skeletal muscle during prolonged running , 1998, The Journal of physiology.

[26]  Alfred Iing Yoong Tok,et al.  Novel biosensor for interleukin-6 detection , 2013 .

[27]  M. Shim,et al.  Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Christoph Nowak,et al.  The extended growth of graphene oxide flakes using ethanol CVD. , 2013, Nanoscale.

[29]  A. M. Rao,et al.  Diameter-Selective Raman Scattering from Vibrational Modes in Carbon Nanotubes , 1997, Science.

[30]  Charles L. Dumke,et al.  Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. , 2003 .

[31]  M. Platt,et al.  The detection and measurement of interleukin-6 in venous and capillary blood samples, and in sweat collected at rest and during exercise , 2014, European Journal of Applied Physiology.

[32]  Bo Liedberg,et al.  Highly manufacturable graphene oxide biosensor for sensitive Interleukin-6 detection , 2015 .

[33]  T. Nussbaumer,et al.  Electrochemical carbon nanotube field-effect transistor , 2000, cond-mat/0009171.

[34]  R. Mooney,et al.  Interleukin-6 induces cellular insulin resistance in hepatocytes. , 2002, Diabetes.

[35]  T. Reid Nanotube arrays: Bridging the gap , 2007 .

[36]  B. Liedberg,et al.  Label-free electronic detection of bio-toxins using aligned carbon nanotubes. , 2013, Biosensors & bioelectronics.