Noise analysis and sensitivity enhancement in immunomagnetic nanomechanical biosensors (original) (raw)
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Physics of Nanomechanical Biosensing on Cantilever Arrays
Advanced Materials, 2008
Living systems that transform biomolecular reactions at the nanoscale into mechanical work at multiple nano-, meso-and macroscopic length scales have inspired the advancing fields of nanotechnology. Cantilever sensors, which integrate 'topdown' miniaturized MEMS devices with 'bottom up' selfassembly of biomolecules, offer the unique ability to convert biomolecular reactions occurring on one side of the cantilever into mesoscopic bending motion for biosensing and smart nanorobotic applications. The differential mode (defined as the bending of the 'active' cantilever minus the bending of an in situ reference cantilever coated with an non-reactive coating) has been shown to be essential for biospecific analysis and exploited experimentally to detect pH, sequence-specific DNA hybridization with single nucleotide polymorphisms, and protein recognition. However, further advances have been limited by a lack of theory underlying the origins of surface stress. For example, both the direction and amplitude of cantilever motion have experimentally been found to depend on the length of the bio-molecule reacting on the cantilever. These effects cannot be explained by the traditional theory developed for macroscopic systems, which ignores the physical properties of the active layer. Therefore, new theoretical approaches need to be developed. Moreover the development of a fundamental theory to identify the key 'figures of merit' will aid the rational design of new coatings and device geometries with significantly improved detection sensitivities for biosensing applications.
Nanomechanical biosensors: a new sensing tool
TrAC Trends in Analytical Chemistry, 2006
Biosensors based on microcantilevers have become a promising tool for directly detecting biomolecular interactions with great accuracy. Microcantilevers translate molecular recognition of biomolecules into nanomechanical motion that is commonly coupled to an optical or piezoresistive read-out detector system. Biosensors based on cantilevers are a good example of how nanotechnology and biotechnology can go together. High-throughput platforms using arrays of cantilevers have been developed for simultaneous measurement and read-out of hundreds of samples. As a result, many interesting applications have been performed and the first sensor platforms are being commercialized. This review covers the basic working principles and the types of sensor format, the fabrication and the reported applications in chemical and biological analysis, trends in cantilever fabrication, examples of the commercial instrumentation available, and future developments. ª
Biosensors based on nanomechanical systems
Chemical Society Reviews, 2013
The advances in micro-and nanofabrication technologies are enabling increasingly smaller mechanical transducers capable of detecting the forces, motion, mechanical properties and masses that emerge in biomolecular interactions and fundamental biological processes. Thus, biosensors based on nanomechanical systems have gained considerable relevance in the last decade. This review provides insight into the mechanical phenomena that occur in suspended mechanical structures when either biological adsorption or interactions take place on their surface. This review guides the reader through the parameters that change as a consequence of biomolecular adsorption: mass, surface stress, effective Young's modulus and viscoelasticity.
Dynamic Actuation of Magnetic Beads for Immunoassays on-chip
2010
This thesis was carried out in the frame of the European project DetectHIV aiming the development of a new biosensor platform for the highly sensitive detection of the HIV capsid protein p24. We explore the implementation of a magnetic bead-based lab-on-a-chip system, offering significant advantages compared to conventional systems, mainly through the possibility of controlled manipulation of the magnetic carriers on-chip. In particular, microfluidic immunoassays using functionalized magnetic beads raise increasing interest. In this thesis, we present a microsystem for the magnetic manipulation of superparamagnetic beads on-chip. A highly confined and dynamically actuated plug of biochemically functionalized beads is formed in a microchannel. This plug extends over the channel cross-section, thus allowing efficient analyte capture from the flow. Subsequent immobilization of the plug for incubation modifies the colloidal state (agglutination test). Dynamic actuation of beads is enabled by superposing a static magnetic field and a time-varying magnetic field. The latter field is highly focused and concentrated across the microchannel by means of soft magnetic microtips. A new method for the fabrication of rigid monolithic SU-8 microchannels allows control and ready mechanical integration of the microtips with the microfluidic structure. A protocol for performing magnetic bead-based immuno-agglutination assays on-chip using our system was developed. A simple detection method based on the swelling of the released plug after agglutination is presented. We demonstrate the feasibility of on-chip agglutination tests by means of a streptavidin/biotinylated-bovine serum albumin (bBSA) model assay. A detection limit of about 200 pg/mL (3 pM) was obtained. Furthermore, the potential of the magnetic actuation method was emphasized by implementing a heterogeneous immunoassay with a dendritic amplification mechanism. Dendritic amplification aims to increase the detection sensitivity. Amplification of the detection signal is achieved by alternating exposure of the beads to a flow of fluorescently labeled streptavidin molecules and biotin conjugated anti-streptavidin, respectively. The magnetic system developed in the frame of this thesis was integrated in the final biosensor platform of the DetectHIV project. This platform comprises an integrated chip cartridge with an optical detection module. This design is outlined in the last part of the thesis.
Biosensors & Bioelectronics, 2003
Small magnetoresistive spin valve sensors (2×6 μm2) were used to detect the binding of single streptavidin functionalized 2 μm magnetic microspheres to a biotinylated sensor surface. The sensor signals, using 8 mA sense current, were in the order of 150–400 μV for a single microsphere depending on sensor sensitivity and the thickness of the passivation layer over the sensor surface. Sensor saturation signals were 1–2 mV representing an estimated 6–20 microspheres, with a noise level of ∼10 μV. The detection of biomolecular recognition for the streptavidin-biotin model was shown using both single and differential sensor architectures. The signal data compares favourably with previously reported signals for high numbers of magnetic microspheres detected using larger multilayered giant magnetoresistance sensors. A wide range of applications is foreseen for this system in the development of biochips, high sensitivity biosensors and the detection of single molecules and single molecule interactions.
Low-noise polymeric nanomechanical biosensors
Applied Physics Letters, 2006
A sensor device based on a single polymer cantilever and optical readout has been developed for detection of molecular recognition reactions without the need of a reference cantilever for subtraction of unspecific signals. Microcantilevers have been fabricated in the photoresist SU-8 with one surface passivated with a thin fluorocarbon layer. The SU-8 surface is sensitized with biological receptors by applying silanization methods, whereas the fluorocarbon surface remains inert to these processes. The thermal and mechanical properties of the chosen materials allow overcoming the main limitations of gold-coated silicon cantilevers: the temperature, pH, and ionic strength cross sensitivities. This is demonstrated by comparing the response of SU-8 cantilevers and that of gold-coated silicon nitride cantilevers to variations in temperature and pH. The sensitivity of the developed polymeric nanomechanical sensor is demonstrated by real-time detection of the human growth hormone with sensitivity in differential surface stress of about 1 mN/ m.
Magnetic properties of nanomagnetic and biomagnetic systems analyzed using cantilever magnetometry
Nanotechnology, 2011
Magnetic properties of nanomagnetic and biomagnetic systems are investigated using cantilever magnetometry. In the presence of a magnetic field, magnetic films or particles deposited at the free end of a cantilever give rise to a torque on the mechanical sensor, which leads to frequency shifts depending on the applied magnetic field. From the frequency response, the magnetic properties of a magnetic sample are obtained. The magnetic field dependences of paramagnetic and ferromagnetic thin films and particles are measured in a temperature range of 5-320 K at a pressure below 10 - 6 mbar. We present magnetic properties of the ferromagnetic materials Fe, Co and Ni at room temperature and also for the rare earth elements Gd, Dy and Tb at various temperatures. In addition, the magnetic moments of magnetotactic bacteria are measured under vacuum conditions at room temperature. Cantilever magnetometry is a highly sensitive tool for characterizing systems with small magnetic moments. By reducing the cantilever dimensions the sensitivity can be increased by an order of magnitude.
Analytical performance and characterization of antibody immobilized magnetoelastic biosensors
Sensing and Instrumentation for Food Quality and Safety, 2008
This article presents the results of an investigation into the enhancement of sensitivity and thermal stability of polyclonal antibody immobilized magnetoelastic biosensors. The Langmuir–Blodgett (LB) monolayer technique was employed for antibody (specific to Salmonella sp.) immobilization on rectangular shaped strip magnetoelastic sensors. Biosensor performance was investigated by exposing to graded concentrations (5 × 101–5 × 108 cfu mL−1) of Salmonella typhimurium solutions in a flow through mode. Bacterial binding to the antibody on the sensor surfaces changed the resonance parameters, and these changes were quantified by the sensor’s resonance frequency shift. An increase in the sensitivity from 159 Hz decade−1 for a 2 mm sensor to 246 Hz decade−1 for a 1 mm sensor was observed during the dose–response measurements. The stability of the biosensor was also investigated by storing the biosensor at 25, 45 and 65 °C. The binding activity of the stored biosensor was estimated by measuring the changes in resonance frequency after exposure to the bacterial solutions (109 cfu mL−1). Binding activity was also confirmed by counting bound S. typhimurium cells on the sensor surface using Scanning Electron Microscopy (SEM) micrographs. The results show that at each temperature, the binding activity of the biosensor gradually decreased over the testing period. Degradation of biosensor accelerated at higher storage temperatures. The activation energy of biosensor system degradation was determined to be 7.7 kcal mol−1.