Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms.
Rapid and multiplexed measurement is vital in the detection of food-borne pathogens. While highly specific and sensitive, traditional immunochemical assays such as enzyme-linked immunosorbent assays (ELISAs) often require expensive read-out equipment (e.g. fluorescent labels) and lack the capability of multiplex detection. By combining the superior specificity of immunoassays with the sensitivity and simplicity of magnetic detection, we have developed a novel multiplex magnetic nanotag-based detection platform for mycotoxins that functions on a sub-picomolar concentration level. Unlike fluorescent labels, magnetic nanotags (MNTs) can be detected with inexpensive giant magnetoresistive (GMR) sensors such as spin-valve sensors. In the system presented here, each spinvalve sensor has an active area of 90 × 90 µm 2 , arranged in an 8×8 array. Sample is added to the antibody-immobilized sensor array prior to the addition of the biotinylated detection antibody. The sensor response is recorded in real time upon the addition of streptavidin-linked MNTs on the chip. Here we demonstrate the simultaneous detection of multiple mycotoxins (aflatoxins B 1 , zearalenone and HT-2) and show that a detection limit of 50 pg/mL can be achieved.
Microfabricated biochips are developed to continuously monitor cell population dynamics in a non-invasive manner. In the presented work we describe the novel combination of contact-less dielectric microsensors and microfluidics to promote biofilm formation for quantitative cell analysis. The cell chip consists of a polymeric fluidic (PDMS) system bonded to a glass wafer containing the electrodes while temperature and fluid flow are controlled by external heating and pumping stations. The high-density interdigitated capacitors (microIDES) are isolated by a 550 nm multi-passivation layer of defined dielectric property and provide stable, robust and non-drifting measurement conditions. The performance of this detector is evaluated using various bacterial and yeast strains. The high sensitivity of the developed dielectric microsensors allows direct identification of microbial strains based on morphological differences and biological composition. The novel biofilm analysis platform is used to continuously monitor the dynamic responses of C. albicans and P. pastoris biofilms to increased shear stress and antimicrobial agent concentration. While the presence of shear stress triggers significant changes in yeast growth profiles, the addition of 0.5 microg mL(-1) amphotericin B revealed two distinct dynamic behaviors of the C. albicans biofilm. Initially, impedance spectra increased linearly at 30 Omega h(-1) for two hours followed by 10 Omega h(-1) (at 50 kHz) over 10 hours while cell viability remained above 95% during fungicide administration. These results demonstrate the ability to directly monitor dielectric changes of sub-cellular components within a living cell population.
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