Abstract
Early-stage detection prevents disease progression and complications in treatment procedures, especially for infectious diseases. This requires rapid and accurate sensing technologies and techniques that remove the need for expensive and time-consuming sample preparation and transfer to the labs and the running of multiple experiments. To that end, point-of-care (POC) testing has been introduced for quick disease diagnostics that enables caregivers to start early treatment, leading to improved health outcomes. Here, we introduce a tunneling current bio-sensing technology based on a metal–insulator–electrolyte junction, which is highly sensitive to charge variations at the insulator–electrolyte interface. The charge variations occur as a response of hybridization of complementary DNA sequences to DNA primers immobilized on the insulator surface. This leads to the label-free detection of as little as tens of DNA molecules or, equivalently, samples with 0.01 fM concentrations. Since the sensing is based on a single terminal measurement of current with respect to a reference electrode, our technology can enable the creation of novel compact medical and portable POC devices for real-time disease detection.
Highlights
Detection and real-time amplification of nucleic acids have profoundly transformed biomedical research and molecular diagnostics, which have a wide range of applications in areas such as quantification of gene expression,1–5 clinical microbiology,6,7 cancer diagnostics,8,9 phytopathology,10,11 and genotyping.12–14The majority of the existing technologies for detection and rapid amplification of DNA molecules require optical sensing in addition to fluorescently labeled sequence-specific probes or fluorescent dyes for labeling DNA molecules,15–19 which makes the devices bulky and expensive, preventing them to be widely accessible by physicians and patients.Over the past decade, highly sensitive nanowire sensors have evolved for detecting molecular (DNA or protein) hybridization.20–23 these sensors require complicated fabrication techniques and the connection of two electrodes to the nanowire to measure the conductance change across the wire
The E-beam evaporation process is performed at UC Irvine Materials Research Institute (IMRI), and all other steps are done at the Integrated Nanosystems Research Facility (INRF) at UC Irvine
We developed a precise charge sensor capable of detecting complementary DNA molecules in solutions with one hundredth of a femtomolar concentration
Summary
Detection and real-time amplification of nucleic acids have profoundly transformed biomedical research and molecular diagnostics, which have a wide range of applications in areas such as quantification of gene expression, clinical microbiology, cancer diagnostics, phytopathology, and genotyping.. Highly sensitive (attomolar) nanowire sensors have evolved for detecting molecular (DNA or protein) hybridization.. Highly sensitive (attomolar) nanowire sensors have evolved for detecting molecular (DNA or protein) hybridization.20–23 These sensors require complicated fabrication techniques and the connection of two electrodes to the nanowire to measure the conductance change across the wire. We show that we can use our tunneling sensor to detect DNA molecules in solutions with concentrations as small as one hundredth of a femtomolar concentration. This technology has the potential to detect attachment of the other charged biomolecules, such as proteins, on the surface.
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