Smart Sensing System for the Prognostic Monitoring of Bone Health

The objective of this paper is to report a novel non-invasive, real-time, and label-free smart assay technique for the prognostic detection of bone loss by electrochemical impedance spectroscopy (EIS). The proposed system incorporated an antibody-antigen-based sensor functionalization to induce selectivity for the C-terminal telopeptide type one collagen (CTx-I) molecules—a bone loss biomarker. Streptavidin agarose was immobilized on the sensing area of a silicon substrate-based planar sensor, patterned with gold interdigital electrodes, to capture the antibody-antigen complex. Calibration experiments were conducted with various known CTx-I concentrations in a buffer solution to obtain a reference curve that was used to quantify the concentration of an analyte in the unknown serum samples. Multivariate chemometric analyses were done to determine the performance viability of the developed system. The analyses suggested that a frequency of 710 Hz is the most discriminating regarding the system sensitivity. A detection limit of 0.147 ng/mL was achieved for the proposed sensor and the corresponding reference curve was linear in the range of 0.147 ng/mL to 2.669 ng/mL. Two sheep blood samples were tested by the developed technique and the results were validated using enzyme-linked immunosorbent assay (ELISA). The results from the proposed technique match those from the ELISA.

[1]  L. Joseph Melton,et al.  Perspective how many women have osteoporosis? , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  S. Gan,et al.  Enzyme immunoassay and enzyme-linked immunosorbent assay. , 2013, The Journal of investigative dermatology.

[3]  Subhas Chandra Mukhopadhyay,et al.  A low cost novel sensing system for detection of dangerous marine biotoxins in seafood , 2009 .

[4]  V. Srivastava,et al.  A New Monoclonal Antibody ELISA for Detection and Characterization of C-telopeptide Fragments of Type I Collagen in Urine , 2001, Calcified Tissue International.

[5]  J. Butler Enzyme-Linked Immunosorbent Assay , 2000, Journal of immunoassay.

[6]  R. Neves,et al.  Corrosion Behavior of Stainless Steel Rebars Embedded in Concrete: an Electrochemical Impedance Spectroscopy Study , 2014 .

[7]  S. C. Mukhopadhyay,et al.  A novel planar interdigital sensor for environmental monitoring , 2009, 2009 IEEE Sensors.

[8]  Joseph M. Lane,et al.  Dynamics of Bone and Cartilage Metabolism. , 2001 .

[9]  Yaofang Hu,et al.  Label-free electrochemical impedance spectroscopy biosensor for direct detection of cancer cells based on the interaction between carbohydrate and lectin. , 2013, Biosensors & bioelectronics.

[10]  Yan Lian,et al.  A new aptamer/graphene interdigitated gold electrode piezoelectric sensor for rapid and specific detection of Staphylococcus aureus. , 2015, Biosensors & bioelectronics.

[11]  I. Ihara,et al.  Coagulation process of soymilk characterized by electrical impedance spectroscopy , 2011 .

[12]  Mark J. Schulz,et al.  A Label-Free Electronic Biosensor for Detection of Bone Turnover Markers , 2009, Sensors.

[13]  Chao Li,et al.  A nanoelectronic enzyme-linked immunosorbent assay for detection of proteins in physiological solutions. , 2010, Small.

[14]  P. Delmas,et al.  Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis , 2008, Osteoporosis International.

[15]  S. Mukhopadhyay,et al.  A Novel Planar-Type Biosensor for Noninvasive Meat Inspection , 2007, IEEE Sensors Journal.

[16]  Kishore Sundara-Rajan,et al.  Interdigital sensors and transducers , 2004, Proceedings of the IEEE.

[17]  S. Mukhopadhyay,et al.  A novel planar interdigital sensor based sensing and instrumentation for detection of dangerous contaminated chemical in seafood , 2009, 2009 IEEE Instrumentation and Measurement Technology Conference.

[18]  R.W. De Doncker,et al.  Modeling the dynamic behavior of supercapacitors using impedance spectroscopy , 2001, Conference Record of the 2001 IEEE Industry Applications Conference. 36th IAS Annual Meeting (Cat. No.01CH37248).

[19]  Michel Fortier,et al.  Osteoporosis in menopause. , 2014, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[20]  C. Hsu,et al.  Technical Note: Concerning the Conversion of the Constant Phase Element Parameter Y0 into a Capacitance , 2001 .

[21]  Chusen Huang,et al.  Highly sensitive electrochemical impedance spectroscopy immunosensor for the detection of AFB1 in olive oil. , 2015, Food chemistry.

[22]  W. Heineman,et al.  Gold-coated carbon nanotube electrode arrays: Immunosensors for impedimetric detection of bone biomarkers. , 2016, Biosensors & bioelectronics.

[23]  Chinthaka P. Gooneratne,et al.  Detection of bacterial endotoxin in food: New planar interdigital sensors based approach , 2013 .

[24]  David A Hanley,et al.  2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary , 2010, Canadian Medical Association Journal.

[25]  Takuya Yokoyama,et al.  Electrochemical impedance spectroscopy biosensor with interdigitated electrode for detection of human immunoglobulin A. , 2013, Biosensors & bioelectronics.

[26]  Leon C. Snyman,et al.  Menopause-related osteoporosis , 2014 .

[27]  Stoyan N. Nihtianov,et al.  Capacitive-Sensor Interface With High Accuracy and Stability , 2009, IEEE Transactions on Instrumentation and Measurement.

[28]  T. S. Ramulu,et al.  Nanowires array modified electrode for enhanced electrochemical detection of nucleic acid. , 2013, Biosensors & bioelectronics.

[29]  Pascal Venet,et al.  Study of Accelerated Aging of Supercapacitors for Transport Applications , 2010, IEEE Transactions on Industrial Electronics.

[30]  Subhas Chandra Mukhopadhyay,et al.  Rapid and molecular selective electrochemical sensing of phthalates in aqueous solution. , 2015, Biosensors & bioelectronics.

[31]  Niina J. Ronkainen,et al.  Immobilization Techniques in the Fabrication of Nanomaterial‐based Electrochemical Biosensors: A Review , 2014 .

[32]  Alaeddin S. Abu-Abed,et al.  CAPACITIVE INTERDIGITAL SENSOR WITH INHOMOGENEOUS NEMATIC LIQUID CRYSTAL FILM , 2008 .

[33]  O. Johnell,et al.  Long-Term Risk of Osteoporotic Fracture in Malmö , 2000, Osteoporosis International.

[34]  S. C. Mukhopadhyay,et al.  Electromagnetic field computation using COMSOL Multiphysics to evaluate the performance of novel interdigital sensors , 2009, 2009 Applied Electromagnetics Conference (AEMC).

[35]  William Putzbach,et al.  Immobilization Techniques in the Fabrication of Nanomaterial-Based Electrochemical Biosensors: A Review , 2013, Sensors.

[36]  R H Christenson,et al.  Biochemical markers of bone metabolism: an overview. , 1997, Clinical biochemistry.