title: A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis.
abstract: Lab-on-a-chip (LOC) devices for electrochemical analysis of DNA hybridization events offer a technology for real-time and label-free assessment of biomarkers at the point-of-care. Here, we present a microfluidic LOC, with 3 × 3 arrayed electrochemical sensors for the analysis of DNA hybridization events. A new dual layer microfluidic valved manipulation system is integrated providing controlled and automated capabilities for high throughput analysis. This feature improves the repeatability, accuracy, and overall sensing performance (Fig. 1). The electrochemical activity of the fabricated microfluidic device is validated and demonstrated repeatable and reversible Nernstian characteristics. System design required detailed analysis of energy storage and dissipation as our sensing modeling involves diffusion-related electrochemical impedance spectroscopy. The effect of DNA hybridization on the calculated charge transfer resistance and the diffusional resistance components is evaluated. We demonstrate a specific device with an average cross-reactivity value of 27.5%. The device yields semilogarithmic dose response and enables a theoretical detection limit of 1 nM of complementary ssDNA target. This limit is lower than our previously reported non-valved device by 74% due to on-chip valve integration providing controlled and accurate assay capabilities.
authors.affiliation: MEMS Sensors and Actuators Laboratory (MSAL), Department of Electrical and Computer Engineering, Institute for Systems Research, University of Maryland, College Park, MD 20742, USA. Electronic address: benyoav@umd.edu.
authors.forename: Hadar
authors.initials: H
authors.lastname: Ben-Yoav
authors.affiliation: MEMS Sensors and Actuators Laboratory (MSAL), Department of Electrical and Computer Engineering, Institute for Systems Research, University of Maryland, College Park, MD 20742, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Dykstra
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
authors.affiliation: MEMS Sensors and Actuators Laboratory (MSAL), Department of Electrical and Computer Engineering, Institute for Systems Research, University of Maryland, College Park, MD 20742, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA. Electronic address: ghodssi@umd.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Ghodssi
mesh_terms: D015374:Biosensing Techniques / Q000295:instrumentation*; D003217:Conductometry / Q000295:instrumentation*; D004247:DNA / Q000032:analysis / Q000235:genetics*; D004058:Diffusion; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005246:Feedback; D017403:In Situ Hybridization / Q000295:instrumentation*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation*; D017422:Sequence Analysis, DNA / Q000295:instrumentation*; D013194:Staining and Labeling
chemical_list: D004247:DNA
keywords: DNA hybridization sensing; Electrochemical impedance spectroscopy; Label-free detection; Microfluidics; Restricted diffusion; Valve