(258f) Electrochemical Biomolecule Sensing by Carbon Nanotubes: Quantification by Warburg Impedance

Development of rapid and portable detection devices for point-of-care application is an important aspect of modern medical diagnostic industry for effective diagnosis of diseases that result in deaths of millions each year in developing countries. Conventional laboratory based microarray technology is relatively slow, employs multistep procedures, and uses bulky and expensive fluorescent detection units operated by trained staff. The cumbersome equipment requirements restrict the usage of such systems to the laboratory settings. Recently, our group developed a electrochemical DNA detection platform with picomolar sensitivity and a 20 minute detection time using equipment that could be easily turned into a hand held, portable device operated by workers with minimal instruction. The system utilizes an open-flow carbon nanotube platform for DNA detection using impedance based sensing of hybridization between target sequences and short oligonucleotide probes. The open flow allows rapid concentration of the target molecules and shear-enhanced specificity. Interdigitated electrodes are used to trap multiwalled carbon nanotubes functionalized with oligonucleotides via amide bonds. Hybridization of the target sequences with the probes changes the electrochemical impedance spectroscopy. In particular, the Warburg element of the electrochemical sensor shows a fingerprint signature, which allows quantification of target molecules captured by the probe-functionalized sensor. The electrochemical spectrum in a batch micro-fluidic chip is easily explained through the Randles circuit, but further circuit elements are needed in the open flow microfluidic chip to account for high-Peclet number mass transfer and target molecule conformation changes due to shear. This accurate analysis of the circuit in the electrochemical sensor gives a quantitative tool to calibrate the DNA concentration in the sample. Here we also expand this platform's capabilities for the detection of RNA and also antibody/antigen. By focusing on RNA, which naturally occurs with a high copy number, PCR or RT PCR steps can be avoided. RNA-DNA duplexes are more stable than their DNA-DNA relatives, so hybridization rates could be enhanced. Further, with antibody/antigen scheme, significant impedance change recorded on addition of antigen to the antibody functionalized CNT, indicates successful binding of antigens. The impedance changes resulting from binding of a multitude of biomolecules to CNTs shows the promise of the platform for a host of point of care diagnostic devices.