Label-free capacitive diagnostics: exploiting local redox probe state occupancy.

An electrode surface confined redox group contributes to a substantial potential-dependent interfacial charging that can be sensitively probed and frequency-resolved by impedance-derived capacitance spectroscopy. In utilizing the sensitivity of this charging fingerprint to redox group environment, one can seek to generate derived sensory configurations. Exemplified here through the generation of mixed molecular films comprising ferrocene and antibody receptors to two clinically important targets, the label-free methodology is able to report on human prostatic acid phosphatase (PAP), a tumor marker, with a limit of detection of 11 pM and C-reactive protein with a limit of detection of 28 pM. Both assays exhibit linear ranges encompassing those of clinical value.

[1]  M. V. van Dieijen-Visser,et al.  A comparative study on the diagnostic value of prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) in patients with carcinoma of the prostate gland. , 1988, Clinica chimica acta; international journal of clinical chemistry.

[2]  Xiliang Luo,et al.  The label free picomolar detection of insulin in blood serum. , 2013, Biosensors & bioelectronics.

[3]  George A Mensah,et al.  CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: overview. , 2004, Circulation.

[4]  P. Schellhammer,et al.  Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass spectral serum profiles discriminates prostate cancer from noncancer patients. , 2002, Clinical chemistry.

[5]  V. Garg,et al.  Role of fetuin‐A in atherosclerosis associated with diabetic patients , 2012, The Journal of pharmacy and pharmacology.

[6]  Wei Yan,et al.  Electrochemical impedance immunosensor based on three-dimensionally ordered macroporous gold film. , 2008, Analytical chemistry.

[7]  J. Kang,et al.  Novel electrical detection of label-free disease marker proteins using piezoresistive self-sensing micro-cantilevers. , 2005, Biosensors & bioelectronics.

[8]  J. Rishpon,et al.  An Electrochemical Immunosensor for C-Reactive Protein Based on Multi-Walled Carbon Nanotube-Modified Electrodes , 2008 .

[9]  N. Rifai,et al.  Evaluation of four automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. , 2000, Clinical chemistry.

[10]  K. Haenen,et al.  Impedimetric, diamond-based immmunosensor for the detection of C-reactive protein , 2011 .

[11]  Yasar Gurbuz,et al.  Label-free RNA aptamer-based capacitive biosensor for the detection of C-reactive protein. , 2010, Physical chemistry chemical physics : PCCP.

[12]  M. H. Meyer,et al.  SPR-based immunosensor for the CRP detection--a new method to detect a well known protein. , 2006, Biosensors & bioelectronics.

[13]  K. O. Pedersen.  Fetuin, a New Globulin Isolated from Serum , 1944, Nature.

[14]  Chad A. LaGrange,et al.  Human Prostatic Acid Phosphatase: Structure, Function and Regulation , 2013, International journal of molecular sciences.

[15]  W. Figg.  Cabazitaxel: filling one of the gaps in the treatment of prostate cancer. , 2010, Cancer biology & therapy.

[16]  Debjani Paul,et al.  Label-free sub-picomolar protein detection with field-effect transistors. , 2010, Analytical chemistry.

[17]  Jason J. Davis,et al.  Sensitive affimer and antibody based impedimetric label-free assays for C-reactive protein. , 2012, Analytical chemistry.

[18]  Jason J. Davis,et al.  An optimised electrochemical biosensor for the label-free detection of C-reactive protein in blood. , 2013, Biosensors & bioelectronics.

[19]  Ryan J. White,et al.  Wash-free, electrochemical platform for the quantitative, multiplexed detection of specific antibodies. , 2012, Analytical chemistry.

[20]  D. Daly,et al.  ELISA microarray technology as a high-throughput system for cancer biomarker validation , 2006, Expert review of proteomics.

[21]  M. Mascini,et al.  Detection of C Reactive Protein (CRP) in Serum by an Electrochemical Aptamer‐Based Sandwich Assay , 2009 .

[22]  E. Aydil,et al.  Polyethylene glycol-coated biocompatible surfaces. , 2000, Journal of biomedical materials research.

[23]  Joseph Wang,et al.  Aptamer biosensor for label-free impedance spectroscopy detection of proteins based on recognition-induced switching of the surface charge. , 2005, Chemical communications.

[24]  Jason J. Davis,et al.  Measuring quantum capacitance in energetically addressable molecular layers. , 2014, Analytical chemistry.

[25]  Jason J. Davis.  Engineering the bioelectronic interface : applications to analyte biosensing and protein detection , 2009 .

[26]  P. Vihko,et al.  Characterization of the principal human prostatic acid phosphatase isoenzyme, purified by affinity chromatography and isoelectric focusing. Part II. , 1978, Clinical chemistry.

[27]  S. Omanovic,et al.  Electrochemical investigations of the interaction of C-reactive protein (CRP) with a CRP antibody chemically immobilized on a gold surface. , 2009, Analytica chimica acta.

[28]  R. Schifman,et al.  Prospective comparison between serum monoclonal prostate specific antigen and acid phosphatase measurements in metastatic prostatic cancer. , 1987, The Journal of urology.

[29]  Dong-Kyung Kim,et al.  Development of indirect-competitive quartz crystal microbalance immunosensor for C-reactive protein , 2009 .

[30]  Sanjeeva Srivastava,et al.  Cancer biomarker detection by surface plasmon resonance biosensors. , 2012, Clinics in laboratory medicine.

[31]  O. Petrii,et al.  Real surface area measurements in electrochemistry , 1991 .

[32]  O. Bodansky,et al.  Reflections on biochemical aspects of human cancer. The Lucy Wortham James Lecture , 1974, Cancer.

[33]  Arun R. Shrivats,et al.  Synthesis of biocompatible PEG-Based star polymers with cationic and degradable core for siRNA delivery. , 2011, Biomacromolecules.

[34]  Jason J. Davis,et al.  A dielectric model of self-assembled monolayer interfaces by capacitive spectroscopy. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[35]  M. Shirmanova,et al.  Novel PEG-organized biocompatible fluorescent nanoparticles doped with an ytterbium cyanoporphyrazine complex for biophotonic applications. , 2010, Chemical communications.

[36]  Xiliang Luo,et al.  Electrical biosensors and the label free detection of protein disease biomarkers. , 2013, Chemical Society reviews.

[37]  Kuei Yuan Tseng,et al.  Immunodetection of pentamer and modified C-reactive protein using surface plasmon resonance biosensing. , 2006, Biosensors & bioelectronics.

[38]  F. Lisdat,et al.  The use of electrochemical impedance spectroscopy for biosensing , 2008, Analytical and bioanalytical chemistry.

[39]  Jason J. Davis,et al.  Capacitance spectroscopy: a versatile approach to resolving the redox density of states and kinetics in redox-active self-assembled monolayers. , 2012, The journal of physical chemistry. B.

[40]  Jason J. Davis,et al.  Label free redox capacitive biosensing. , 2013, Biosensors & bioelectronics.

[41]  N. Azumi,et al.  Prostatic Acid Phosphatase in Carcinoid Tumors: Immunohistochemical and Immunoblot Studies , 1991, The American journal of surgical pathology.

[42]  Jason J. Davis,et al.  Elucidating capacitance and resistance terms in confined electroactive molecular layers. , 2013, Analytical chemistry.

[43]  A. SolerRoselló,et al.  Clinical behavior of prostatic specific antigen and prostatic acid phosphatase: a comparative study. , 1988 .

[44]  K. Pavey.  Quartz crystal analytical sensors: the future of label-free, real-time diagnostics? , 2002, Expert review of molecular diagnostics.

[45]  M. Aldissi,et al.  Challenges of electrochemical impedance spectroscopy in protein biosensing. , 2009, Analytical chemistry.

[46]  N. Pourmand,et al.  Label-Free Impedance Biosensors: Opportunities and Challenges. , 2007, Electroanalysis.