Thomas Thundat

Bioassay of prostate-specific antigen (PSA) using microcantilevers.

Diagnosis and monitoring of complex diseases such as cancer require quantitative detection of multiple proteins. Recent work has shown that when specific biomolecular binding occurs on one surface of a microcantilever beam, intermolecular nanomechanics bend the cantilever, which can be optically detected. Although this label-free technique readily lends itself to formation of microcantilever arrays, what has remained unclear is the technologically critical issue of whether it is sufficiently specific and sensitive to detect disease-related proteins at clinically relevant conditions and concentrations. As an example, we report here that microcantilevers of different geometries have been used to detect two forms of prostate-specific antigen (PSA) over a wide range of concentrations from 0.2 ng/ml to 60 μg/ml in a background of human serum albumin (HSA) and human plasminogen (HP) at 1 mg/ml, making this a clinically relevant diagnostic technique for prostate cancer. Because cantilever motion originates from the free-energy change induced by specific biomolecular binding, this technique may offer a common platform for high-throughput label-free analysis of protein–protein binding, DNA hybridization, and DNA–protein interactions, as well as drug discovery.

Adsorption-induced surface stress and its effects on resonance frequency of microcantilevers

It is well known that bimetallic microcantilevers can exhibit static deflection as a result of thermal effects, including exothermic adsorption of chemicals on their surfaces. It is shown here that the resonance frequency of a cantilever can change due to a combination of mass loading and change of spring constant resulting from adsorption of chemicals on the surface. Cantilevers also undergo static bending that is induced by differential surface stress. The magnitude of these effects depends upon the chemical properties of the surface and upon the amount of material adsorbed. Hence cantilever deflection as well as resonance frequency change can be used as the basis for development of novel chemical sensors.

Detection of mercury vapor using resonating microcantilevers

Oscillating silicon nitride microcantilevers coated with a thin gold film have been used to detect mercury vapor in air. Cantilever resonance frequency changes due to surface mass loading as a result of adsorption of mercury vapor. Furthermore, cantilever bending is also altered due to changes in surface stress induced by mercury adsorption on the gold overlayer. Both of these phenomena can be used to quantitatively detect adsorbed vapors with picogram mass resolution.

THERMAL AND AMBIENT-INDUCED DEFLECTIONS OF SCANNING FORCE MICROSCOPE CANTILEVERS

The deflection of scanning force microscope cantilevers, metal coated on one side, is significantly influenced by both thermal heating and variations in relative humidity. For constant relative humidity, the deflection of the cantilever drifts due to laser heating and eventually reaches a steady‐state value. For a thermally stabilized cantilever, the deflection varies linearly with relative humidity. Exposure to other vapors, such as mercury, changes the inherent deflection of the cantilever. Relative amounts of adsorbates on the cantilever can be estimated from shifts in the cantilever resonance frequency with picogram mass resolution. The cantilever deflection as well as changes in resonance frequency due to vapor adsorption can be used as basis for novel chemical sensors.

Resonance response of scanning force microscopy cantilevers

A variational method is used to calculate the deflection and the fundamental and harmonic resonance frequencies of commercial V‐shaped and rectangular atomic force microscopy cantilevers. The effective mass of V‐shaped cantilevers is roughly half that calculated for the equivalent rectangular cantilevers. Damping by environmental gases, including air, nitrogen, argon, and helium, affects the frequency of maximum response and to a much greater degree the quality factor Q. Helium has the lowest viscosity, resulting in the highest Q, and thus provides the best sensitivity in noncontact force microscopy. Damping in liquids is dominated by an increase in effective mass of the cantilever due to an added mass of the liquid being dragged with that cantilever.

Nanosensors for trace explosive detection

Selective and sensitive detection of explosives is very important in countering terrorist threats. Detecting trace explosives has become a very complex and expensive endeavor because of a number of factors, such as the wide variety of materials that can be used as explosives, the lack of easily detectable signatures, the vast number of avenues by which these weapons can be deployed, and the lack of inexpensive sensors with high sensitivity and selectivity. High sensitivity and selectivity, combined with the ability to lower the deployment cost of sensors using mass production, is essential in winning the war on explosives-based terrorism. Nanosensors have the potential to satisfy all the requirements for an effective platform for the trace detection of explosives.Selective and sensitive detection of explosives is very important in countering terrorist threats. Detecting trace explosives has become a very complex and expensive endeavor because of a number of factors, such as the wide variety of materials that can be used as explosives, the lack of easily detectable signatures, the vast number of avenues by which these weapons can be deployed, and the lack of inexpensive sensors with high sensitivity and selectivity. High sensitivity and selectivity, combined with the ability to lower the deployment cost of sensors using mass production, is essential in winning the war on explosives-based terrorism. Nanosensors have the potential to satisfy all the requirements for an effective platform for the trace detection of explosives.

Sensitive detection of plastic explosives with self-assembled monolayer-coated microcantilevers

We report the detection of 10–30 parts-per-trillion levels of pentaerythritol tetranitrate and hexahydro-1,3,5-triazine within 20 s of exposure to a silicon microcantilever with its gold surface modified with a self-assembled monolayer of 4-mercaptobenzoic acid. These measurements correspond to a limit of detection of a few fg.

Preparation and characterization of STM tips for electrochemical studies

We report on a fabrication technique for scanning tunneling microscopy (STM) tips for in situ electrochemical investigations. Unwanted Faradaic currents were minimized by insulating the STM tips with Apiezon wax. Cyclic voltammetry showed Apiezon wax to be inert in various electrolytes.

Explosives: A microsensor for trinitrotoluene vapour

Sensing devices designed to detect explosive vapours are bulky, expensive and in need of technological improvement — dogs remain the most effective detectors in the fight against terrorism and in the removal of land-mines. Here we demonstrate the deflagration of trinitrotoluene (TNT) in a small localized explosion on an uncoated piezoresistive microcantilever. This explosive-vapour sensor, which has a detection capability that is comparable to that of a dog, should enable extremely sensitive, miniature detection devices to be used on a large scale.

Viscous drag measurements utilizing microfabricated cantilevers

The influence of viscous drag forces on cantilevers is investigated using standard atomic force microscope (AFM) cantilevers. Viscosity effects on several geometrically different cantilevers manifest themselves as variations in resonance frequencies, quality factors, and cantilever response amplitudes. With this novel measurement, a single cantilever can be used to measure viscosities ranging from η=10−2 to 102 g/cm s.