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Biomedical subjects

Thomas Thundat

Publications and source records attributed to Thomas Thundat.

At least 19 recordsLinked to original sources

Effective mass and flow patterns of fluids surrounding microcantilevers.

An analytical approach to determine the streamlines of fluid flow adjacent to the surfaces of vibrating cantilevers is presented. Fluid flow over the top and bottom surfaces of a microcantilever is established by solving two-dimensional Navier-Stokes equations for viscous flow. The x and y velocity components are used to establish streamlines for absolute fluid motion. These streamlines show a central stagnation core perpendicular and central to the cantilever surface extending along the full length of cantilevers, which most likely accounts for the added mass effect (induced mass) of fluid media around vibrating microcantilevers.

Air↗

Effect of nanometer surface morphology on surface stress and adsorption kinetics of alkanethiol self-assembled monolayers.

Microcantilevers undergo quasi-static bending due to adsorption-induced stress when adsorption is confined to a single surface. Understanding the origin of surface stress is crucial for optimizing sensor performance. We have investigated the effect of surface morphology of gold-coated cantilevers on the adsorption characteristics of self-assembled monolayers of alkanethiols. Self-assembly of alkanethiols from liquid phase closely follows Langmuir-type kinetics up to a single monolayer assembly. Our results indicate that alkanethiol adsorption-induced surface stress is largely unaffected by surface roughness of the cantilever. Unlike prior reports that suggest surface roughness enhances adsorption-induced stress, we observe that nanometer-size roughness slightly decreases surface stress and adsorption kinetics.

Alkanes↗

Optically directed molecular transport and 3D isoelectric positioning of amphoteric biomolecules.

We demonstrate the formation of charged molecular packets and their transport within optically created electrical force-field traps in a pH-buffered electrolyte. We call this process photoelectrophoretic localization and transport (PELT). The electrolyte is in contact with a photoconductive semiconductor electrode and a counterelectrode that are connected through an external circuit. A light beam directed to coordinates on the photoconductive electrode surface produces a photocurrent within the circuit and electrolyte. Within the electrolyte, the photocurrent creates localized force-field traps centered at the illuminated coordinates. Charged molecules, including polypeptides and proteins, electrophoretically accumulate into the traps and subsequently can be transported in the electrolyte by moving the traps over the photoconductive electrode in response to movement of the light beam. The molecules in a single trap can be divided into aliquots, and the aliquots can be directed along multiple routes simultaneously by using multiple light beams. This photoelectrophoretic transport of charged molecules by PELT resembles the electrostatic transport of electrons within force-field wells of solid-state charge-coupled devices. The molecules, however, travel in a liquid electrolyte rather than a solid. Furthermore, we have used PELT to position amphoteric biomolecules in three dimensions. A 3D pH gradient was created in an electrolyte medium by controlling the illumination position on a photoconductive anode where protons were generated electrolytically. Photoelectrophoretic transport of amphoteric molecules through the pH gradient resulted in accumulation of the molecules at their apparent 3D isoelectric coordinates in the medium.

Animals↗

Nanotechnologies for biomolecular detection and medical diagnostics.

Nanotechnology-based platforms for the high-throughput, multiplexed detection of proteins and nucleic acids in heretofore unattainable abundance ranges promise to bring substantial advances in molecular medicine. The emerging approaches reviewed in this article, with reference to their diagnostic potential, include nanotextured surfaces for proteomics, a two-particle sandwich assay for the biological amplification of low-concentration biomolecular signals, and silicon-based nanostructures for the transduction of molecular binding into electrical and mechanical signals, respectively.

Biopolymers↗

Nanopowder molding method for creating implantable high-aspect-ratio electrodes on thin flexible substrates.

Metal nanoparticles and a nanopowder molding process were used to fabricate 2D and 3D patternable structures having a height-to-width ratio of up to 10:1. By means of this process, an entire neural stimulation circuit, including stimulating electrode, connection trace, and contact pad, can be fused into one continuous, integrated structure where different sections can have different heights, widths, and shapes. The technique is suitable for mass production, and the fabricated electrode is robust and very flexible. More importantly for biomedical applications, the entire fabricated structure can be packed at room temperature onto a biocompatible flexible substrate, such as polydimethylsiloxane, parylene, and polyimide as well as other temperature-sensitive or vacuum-sensitive materials. The electrodes and wires have about the same electrical resistivities as bulk materials and desirable electrochemical properties, including low impedance.

Electric Capacitance↗

Locally enhanced relative humidity for scanning probe nanolithography.

The formation of a water meniscus between a sharp tip and a solid surface is one of the prevailing requirements for scanning probe microscope (SPM)-based lithographies, such as dip-pen nanolithography (DPN) and conductive tip induced oxidation. The water meniscus functions as a medium for the oxidation of or mass transfer to the solid surface. Here we report a simple, efficient, and effective approach to enhance the local relative humidity and thus increase the size of the water meniscus by bringing a water-containing capillary tube to the proximity of the tip-surface contact area. The enhancement in local relative humidity is confirmed via an increase in the measured tip-surface adhesion forces and the widths of DPN generated parallel lines. Compared to the global control of relative humidity for the whole lithography system, the short distance between the "water reservoir" and the tip-surface contact area enables rapid increase in the local vapor pressure of water, less perturbation, and minimal erosion to the state-of-the-art electronics. As a result, most scanning probe lithography experiments at high relative humidity can now be performed in a reasonable time frame.

Letter↗

Microcantilever biosensors.

Biosensors are sensors in which biomolecular interactions are used as sensing reactions. Biomolecular interactions, when combined with a microcantilever platform, can produce an extremely powerful biosensing design. The resonance frequency of a microcantilever shifts sensitively due to mass loading from molecular interaction as in the case of any acoustic sensors. In addition, the microcantilevers also undergo bending if the molecular adsorption is confined to a single surface of a microcantilever. This cantilever bending is due to a differential surface stress caused by the forces involved in the adsorption process and is amplified by making the cantilever surfaces chemically different. Lack of specificity, the main disadvantage of the cantilevers, can be overcome by using the extremely selective biochemical reactions such as receptor-ligand, antibody-antigen, or enzyme-substrate reactions. Here we review the microcantilever technology and discuss a number of highly sensitive biochemical sensor applications based on microcantilevers.

Adsorption↗

Dynamic microcantilever sensors for discerning biomolecular interactions.

Response of a conductive micromechanical cantilever placed in close proximity to a surface undergoing electrical excitation near the resonance frequency of the cantilever is influenced by the presence of microscopic dielectrics in the gap between the cantilever and the sample surface. The variations of the resonance response of unmodified cantilevers at gap distances below a few hundred nanometers are used to discern biomolecular differences of oligomeric nucleic acids in an array format without the use of extrinsic labels. The resonance response variation paves the way for the development of high throughput detection of biomolecular reactions, such as DNA hybridization reactions or antibody-antigen interactions without the use of external labels, in which the need is only to see the presence or absence of interaction. This dynamic method is simple, does not require immobilizing individual elements on a cantilever array, and is compatible with current generation DNA chips in which DNA spots are deposited in micro- and nanoarray format.

Biosensing Techniques↗

Synthesis, characterization, and optical properties of AuSe nanoalloys.

A solution phase approach to synthesize a new metal-semiconductor nanocomposite, AuSe nanoalloy has been reported. The synthesis has been achieved through UV-photoactivation of preformed Au and Se nanoparticles in micelle. Non-ionic surfactant Triton X-100 was exploited as a micellar medium for effective fusion of gold and selenium particles under UV. Both physical and chemical studies have been performed to characterize the composition and morphology of the particles. UV-visible, TEM, SEM, XPS and AFM analyses were done for characterization purpose. The optical properties of nanocomposites have been substantiated through their interaction with a fluorescent probe, eosin in aqueous solution. The spectroscopic investigation of dye-metal-semiconductor assembly has been examined critically. It has been found that the dye experiences J and H types of aggregation on the surfaces of gold and selenium nanoparticles respectively. Again, the composition dependent change of the emission profile of the probe on different nanocomposite surfaces has been rationalized in accordance with the molecular dimerization of the dye.

Alloys↗

Photon-driven nanomechanical cyclic motion.

Microcantilevers modified by a monolayer of azobenzene molecules bend up and down periodically, switched by a 365 nm UV light, as a result of the conversion of the two configurations of azobenzene molecules in the monolayer.

Journal Article↗

Detection of femtomolar concentrations of HF Using an SiO(2) microcantilever.

Femtomolar concentrations of hydrogen fluoride, a decomposition component of nerve agents, were detected using a SiO(2) microcantilever. The microcantilever underwent bending due to the reaction of HF with SiO(2). The microcantilever deflection increased as the concentration of HF increased. Other acids, such as HCl, had no effect on the deflection of the cantilever. The mechanism of reaction-induced bending and the correlation of microcantilever deflection with the HF concentration are discussed. The deflection in response to HF of a commercially available silicon cantilever was also studied, and its response was compared with that of the SiO(2) cantilever. Much less bending amplitude and sensitivity were observed for the silicon cantilever.

Biosensing Techniques↗

Glucose biosensor based on the microcantilever.

Diagnosis and management of diabetes require quantitative and selective detection of blood glucose levels. We report a technique for micromechanical detection of biologically relevant glucose concentrations by immobilization of glucose oxidase (GOx) onto a microcantilever surface. Microfabricated cantilevers have traditionally found utility in atomic force microscope imaging. During the past decade, however, microcantilevers have been increasingly used as transducers in chemical-sensing systems. This paper describes the combination of this technology with enzyme specificity to construct a highly selective glucose biosensor. The enzyme-functionalized microcantilever undergoes bending due to a change in surface stress induced by the reaction between glucose in solution and the GOx immobilized on the cantilever surface. Experiments were carried out under flow conditions. The common interferences for glucose detection in other detection schemes have been tested and have shown to have no effect on the measurement of blood glucose level by this technique.

Biosensing Techniques↗

Molecular recognition of biowarfare agents using micromechanical sensors.

Recent terrorist events have demonstrated that an urgent and widespread need exists for the development of novel sensors for threat detection, especially biowarfare agents. The advent of inexpensive, mass-produced microcantilever sensors promises to bring about a revolution in detection of terrorist threats. Extremely sensitive and highly selective sensors can be developed for using a microcantilever platform. Microcantilevers undergo bending when molecules are adsorbed on a single side. For biowarfare agent detection, specificity is achieved by immobilizing antibodies on one side of the cantilever. Antigen adsorption decreases surface energy and stress, resulting in cantilever deflection.

Antibodies, Bacterial↗

Detection of heavy metal ions using protein-functionalized microcantilever sensors.

Microcantilevers functionalized with metal-binding protein, AgNt84-6, are demonstrated to be sensors for the detection of heavy metal ions like Hg(2+) and Zn(2+). AgNt84-6, a protein that has the ability to bind multiple atoms of Ni(2+), Zn(2+), Co(2+), Cu(2+), Cd(2+) and Hg(2+) was attached to the gold-coated side of silicon nitride cantilevers via linker groups. Upon exposure to 0.1 mM HgCl(2) and 0.1 mM ZnCl(2) solutions, the microcantilevers underwent bending corresponding to an expanding gold side. Exposure to a 0.1 mM solution of MnCl(2) solution did not result in a similar bending indicating a weak or no interaction of Mn(2+) ions with the AgNt84-6 protein. The microcantilever bending data were consistent with data from electrophoresis carried out on SDS-PAGE gels containing metal ions that showed protein interaction with Zn(2+) ions but not with Mn(2+) ions. Thus, we demonstrate that microcantilever bending can be used to discriminate between metal ions that bind and do not bind to AgNt84-6 protein in real time.

Biosensing Techniques↗

Detection of CrO4(2-) using a hydrogel swelling microcantilever sensor.

Hydrogels containing various mounts of tetraalkylammonium salts were used to modify microcantilevers for measurements of the concentration of CrO4(2-) in aqueous solutions. These microcantilevers undergo bending deflection upon exposure to solutions containing various CrO4(2-) concentrations as a result of swelling or shrinking of the hydrogels. The microcantilever deflection as a function of the concentration of CrO4(2-) ions is nearly linear in most concentration ranges. It was found that a concentration of 10(-11) M CrO4(2-) can be detected using this technology in a fluid cell. Other ions, such as Br-, HPO4(2-), and NO3-, have minimal effect on the deflection of this cantilever. The anions SO4(2-) and CO3(2-) could interfere with the CrO4(2-) detection, but only at high concentrations (> 10(-5) M). Such hydrogel-coated microcantilevers could potentially be used to prepare microcantilever-based chemical and biological sensors when molecular recognition agents are immobilized in the hydrogel.

Journal Article↗

Size-correlated spectroscopy and imaging of rare-earth-doped nanocrystals.

Isolated europium-doped metal-oxide nanoparticles were probed by size-correlated high-numerical-aperture (far-field) imaging techniques. A modified Digital Instruments Bioscope atomic force microscope mounted upon a Nikon TE300 inverted microscope was used to interrogate (dry) particles ranging in size from 2 to 150 nm on the surface of a glass or quartz coverslip. These experiments revealed several interesting features of doped-nanoparticle luminescence such as Poissonian occupation statistics, size-dependent luminescence efficiency enhancement for particle sizes of <10 nm, and correlation of interesting transient behavior at particle sizes of <5 nm.

Journal Article↗