285 research outputs found

    Development of microcantilever sensors for cell studies

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    Micro- and nano- electromechanical devices such as microcantilevers have paved the way for a large variety of new possibilities, such as the rapid diagnosis of diseases and a high throughput platform for drug discovery. Conventional cell assay methods rely on the addition of reagents, disrupting the measurement, therefore providing only the endpoint data of the cell growth experiment. In addition, these methods are typically slow to provide results and time and cost consuming. Therefore, microcantilever sensors are a great platform to conduct cell culturing experiments for cell culture, viability, proliferation, and cytotoxicity monitoring, providing advantages such as being able to monitor cell kinetics in real time without requiring external reagents, in addition to being low cost and fast, which conventional cell assay methods are unable to provide. This work aims to develop and test different types of microcantilever biosensors for the detection and monitoring of cell proliferation. This approach will overcome many of the current challenges facing microcantilever biosensors, including but not limited to achieving characteristics such as being low cost, rapid, easy to use, highly sensitive, label-free, multiplexed arrays, etc. Microcantilever sensor platforms utilizing both a single and scanning optical beam detection methods were developed and incorporated aspects such as temperature control, calibration, and readout schemes. Arrays of up to 16 or 32 microcantilever sensors can be simultaneously measured with integrated microfluidic channels. The effectiveness of these cantilever platforms are demonstrated through multiple studies, including examples of growth induced bending of polyimide cantilevers for simple real-time yeast cell measurements and a microcantilever array for rapid, sensitive, and real-time measurement of nanomaterial toxicity on the C3A human liver cell line. In addition, other techniques for microcantilever arrays and microfluidics will be presented along with demonstrations for the ability for stem cell growth monitoring and pathogen detection

    NONLINEAR MODELING OF THE ADSORPTION-INDUCED SURFACE STRESS IN PIEZOELECTRICALLY-DRIVEN MICROCANTILEVER BIOSENSORS

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    Microcantilever-based biosensors are rapidly becoming an enabling sensing technology for a variety of label-free biological applications due to their extreme applicability, versatility and low cost. These sensors operate through the adsorption of species on the functionalized surface of microcantilevers. The adsorption of biological species induces surface stress which originates from the molecular interactions such as adhesion forces of attraction/repulsion, electrostatic forces or the surface charge redistribution of the underlying substrate. This surface stress, consequently, alters the resonance frequency of the microcantilever beam. This study presents a general framework towards modeling resonance frequency changes induced due to the surface stress arising from the adsorption of biological species on the surface of the microcantilever. Very few works have dealt with the effect of surface stress on the resonance frequency shifts of microcantilevers and mainly assume a simple model for the vibrating microcantilever beam. In the proposed modeling framework, the nonlinear terms due to beam\u27s flexural rigidity from macro- to micro-scale as well as varying nature of the adsorption induced surface stress are considered. It is first shown that the nonlinearity of the system originates from two different sources; namely, microcantilever flexural rigidity and adsorption induced surface stress. All these nonlinearities are formulated into the general equation of motion of the vibrating microcantilever. It is then shown that the dynamic mode of biosensing formulated in the paper is much more sensitive than the static mode to the change in the properties of the adsorbed biological species

    Microcantilever biosensors

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    The cross-sensitivity of microcantilever sensors presents a major obstacle in the development of a commercially viable microcantilever biosensor for point of care testing. This thesis concerns electrothermally actuated bi-material microcantilevers with piezoresistive read out, developed for use as a blood coagulometer. Thermal properties of the sensor environment including the heat capacity and thermal conductivity affect the ‘thermal profile’ onto which the higher frequency mechanical signal is superimposed. In addition, polymer microcantilevers are known to have cross-sensitivity to relative humidity due to moisture absorption in the beam. However it is not known whether any of these cross sensitivities have a significant impact on performance of the sensor during pulsed mode operation or following immersion into liquid. When analysing patient blood samples, any change in signal that is not caused by the change in blood viscosity during clotting could lead to a false result and consequently an incorrect dose of anticoagulants may be taken by the patient. In order to address these issues three aspects of the operation of polymer bi-material strip cantilevers has been researched and investigated: relative humidity; viscosity/density, and thermal conductivity of a liquid environment. The relative humidity was not found to affect the resonant frequency of a microcantilever operated in air, or to affect the ability of the cantilever to measure clot times. However, a decrease in deflection with increasing relative humidity of the SmartStrip microcantilever beams is observed at 1.1 ± 0.4 μm per 1% RH, and is constant with temperature over the range 10 – 37 °C, which is an issue that should be considered in quality control. In this study, the SmartStrip was shown to have viscosity sensitivity of 2 cP within the range 0.7 – 15.2 cP, and it was also shown that the influence of inertial effects is negligible in comparison to the viscosity. To investigate cross-sensitivity to the thermal properties of the environment, the first demonstration of a cantilever designed specifically to observe the thermal background is presented. Characterisation experiments showed that the piezoresistive component of the signal was minimised to -0.8% ± 0.2% of the total signal by repositioning the read out tracks onto the neutral axis of the beam. Characterisations of the signal in a range of silicone oils with different thermal conductivities gave a resolution to thermal conductivity of 0.3 Wm-1K-1 and resulted in a suggestion for design improvements in the sensor: the time taken for the thermal background signal to reach a maximum can be increased by increasing the distance between the heater and sensor, thus lessening the impact of the thermal crosstalk within the cantilever beam. A preliminary investigation into thermal properties of clotting blood plasma showed that the sensor can distinguish the change between fresh and clotted plasma

    Hybrid structures for molecular level sensing

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    With substantial molecular mobility and segment dynamics relative to metals and ceramics, all polymeric materials, to some extent, are stimuli-responsive by exhibiting pronounced chemical and physical changes in the backbone, side chains, segments, or end groups induced by changes in the local environment. Thus, the push to incorporate polymeric materials as sensing/responsive nanoscale layers into next-generation miniaturized sensor applications is a natural progression. The significance and impact of this research is wide-ranging because it offers design considerations and presents results in perhaps two of the most critical broad areas of nanotechnology: ultrathin multifunctional polymer coatings and miniaturized sensors. In this work, direct evidence is given showing that polymer coatings comprised of deliberately selected molecular segments with very different chemistry can have switchable properties, and that the surface composition can be precisely controlled, and thus properties can be tuned: all in films on the order of 20 nm and less. Furthermore, active sensing layers in the form of plasma-polymerized polymers are successfully incorporated into actual silicon based microsensors resulting in a novel hybrid organic/inorganic materials platform for microfabricated MEMS sensors with record performance far beyond contemporary sensors in terms of detection sensitivity to various environments. The results produced in this research show thermal sensors with more than two orders of magnitude better sensitivity than what is attainable currently. In addition, a humidity response on the order of parts per trillion, which is four orders of magnitude more sensitive than current designs is achieved. Molecular interactions and forces for organic molecules are characterized at the picoscale to optimize polymeric nanoscale layer design that in turn optimize and lead to microscale hybrid sensors with unprecedented sensitivities
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