There is an acute need for the development of a new class of selective and sensitive portable analytical sensors to enable reliable monitoring of multiple classes of chemical analytes in complex biomatrices. Current preferred methods for determining the concentration of analytes are spectroscopy and voltammetry. We propose the development of electrochemical microarray sensors using boron-doped ultrananocrystalline diamond (UNCD) that promise superior sensitivity and specificity, fast response time, low background currents and resistance to surface fouling as compared to the current standard electrode materials, e.g. metal and sp2 carbon. The goal of this proposal is to develop a highly multiplexed UNCD microarray technology for simultaneous monitoring of multiple classes of analytes, especially with very low sample volumes. The specific aims of this proposal are to: (i) demonstrate microelectrode electrochemical behavior (i.e. higher S/N ratio) of a 3¿3 UNCD microarray using cyclic voltammetry (ii) demonstrate model analyte detection selected from three major class of analytes viz. toxic metals, endocrine-disrupting compounds (EDCs) and endotoxins on a modified UNCD microarray and (iii) demonstrate the unique advantages of multiplexed UNCD microarrays by measuring all three model analytes (i.e. lead, estradiol and lipopolysaccharide) in simple bio fluids (e.g. serum), which is an important step towards simultaneous multi-analyte detection. As a proof-of-concept demonstration, the microarrays will be used to analyze solutions of these model analytes at or near clinically- relevant concentrations (<100 ppb) in saline solution. The proposed microarray chemical sensor could potentially be applied to the simultaneous analysis of solutions of heavy metals, EDCs, insecticides, toxins and many other important chemicals in clinical samples. If this project is successful, it will address several key NIEHS mission goals, specifically: portability, enhanced detection sensitivity for clinically relevant analytes and versatility to allow the detection platfrm a widest range of possible analytes. The portability is readily achievable because of multiplexed UNCD microarrays can be fabricated in less than 1mm¿1mm footprint. This tiny footprint also enhances sensitivity by orders of magnitude due to their intrinsically low backgrounds currents and UNCD's unique surface chemistry. Finally, UNCD electrode surfaces modified with SAMs, enzymes, antibodies and oligonucleotide probes can detect a wider range of chemical analytes than any other electrode material. These superlative sensing capabilities have significant commercial implications. Based on a letter of support from a leading nanoArray company, the expected annual sales for this product would be "at least $50 million" and would be expected to exceed this number many-fold over the broader clinical sensor market which is at least $10.9 billion based on a recent market survey. Also, a greater understanding of selective sensing would enable alternative applications for the technology, including: low-cost, chronic, in vivo sensors for neurotransmitters, alcohol, metabolites and disease biomarkers.
Public Health Relevance Statement: Public Health Relevance: This project will develop a microarray sensor technology using ultrananocrystalline diamond electrodes to further advance personal biomonitoring. Its versatility, sensitivity, specificity and reliability are ideally suited for measurement of multipl classes of chemicals.
Project Terms: Acute; Address; Aftercare; Age; Alcohols; Antibodies; base; Behavior; Biological Markers; Biological Monitoring; Blood; Boron; Brain; Buffers; Caliber; Calibration; Carbon; Carbon Nanotubes; Cessation of life; Chemicals; Chemistry; Child; Chronic; Clinical; clinically relevant; Complex; cost; cross reactivity; Data; Deposition; Detection; Development; Diamond; Diffusion; Disease; Electric Capacitance; Electrodes; Endocrine Disruptors; Endotoxins; Enzymes; Estradiol; estrogenic activity; Fast Electron; Film; Goals; Goat; Heavy Metals; Immune; improved; In Vitro; in vivo; Insecticides; Kinetics; Lead; Learning Disabilities; Letters; Lipopolysaccharides; Liquid substance; Marketing; Measurement; Measures; Metals; Methods; Metric; Microarray Analysis; Microelectrodes; Mission; Modeling; Modification; Monitor; Nanoarray Analytical Device; National Institute of Environmental Health Sciences; Neurotransmitters; Noise; Oligonucleotide Probes; Paste substance; Performance; Phase; Polymyxin B; portability; Problem behavior; Process; Property; public health relevance; Reaction Time; Reproducibility; Resistance; Sales; Saline; Saliva; Sampling; scale up; Sensitivity and Specificity; sensor; Sepsis; Serine; Serum; Signal Transduction; Silicon; Solutions; Spectrum Analysis; Surface; Surveys; Technology; Testing; toxic metal; Toxin; United States; Urin
