Micro- and nanoelectromechanical systems, including cantilevers and other small scale structures, have been studied for sensor applications. Accurate sensing of gaseous or aqueous environments, chemical vapors, and biomolecules have been demonstrated using a variety of these devices that undergo static deflections or shifts in resonant frequency upon analyte binding. In particular, biological detection of viruses, antigens, DNA, and other proteins is of great interest. While the majority of currently used detection schemes are reliant on biomarkers, such as fluorescent labels, time, effort, and chemical activity could be saved by developing an ultrasensitive method of label-free mass detection. Micro- and nanoscale sensors have been effectively applied as label-free detectors. In the following, we review the technologies and recent developments in the field of micro- and nanoelectromechanical sensors with particular emphasis on their application as biological sensors and recent work towards integrating these sensors in microfluidic systems.

In this work, we use arrays of nanomechanical resonators to detect prostate specific antigen (PSA), a protein biomarker associated with prostate cancer. The surfaces of our very thin, trampoline-like devices are functionalized for immunospecific capture of PSA molecules, and the mass of bound material can be detected as a reduction in the resonant frequency. Fetal bovine serum was spiked with known concentrations of PSA, and in conjunction with a nanoparticle-based sandwich assay, concentrations as low as 50 fg mL(-1), or 1.5 fM, could be detected from the realistic samples. The presence of non-specific proteins in the serum did not significantly affect the sensitivity of our assay.

Physical vapor deposition onto rare gas buffer layers leads to the spontaneous formation of clusters. During the thermal desorption of the buffer, these clusters diffuse and aggregate into larger structures, a process known as buffer-layer-assisted growth and desorption assisted coalescence. We studied the effect of buffer thickness and the rate of buffer desorption on the extent of this aggregation for Ag, Au, Cu, Pd, Co, and Ni particles on a solid Xe surface. On the basis of these experiments, results from Monte Carlo simulations and the existing theoretical models for cluster-cluster aggregation, we report for the first time the Arrhenius parameters for nanoparticle slip-diffusion. The effective activation energies range from 0.12 for small Ag clusters (few hundred atoms) to 0.60 eV for ramified Ni islands (millions of atoms), and the giant pre-exponential factors were found to differ by many orders of magnitude. Significantly, the pre-exponential factors follow a Meyer-Neldeltype dependence on the corresponding effective activation energy, with a characteristic Meyer-Neldel energy of 6.9 meV. This energy is associated with the phononic excitations in solid Xe that are responsible for nanostructure mobility. This dependence should be a characteristic feature of nanoparticle diffusion.

Nanomechanical resonators have shown potential application for mass sensing and have been used to detect a variety of biomolecules. In this study, a dynamic resonance-based technique was used to detect prion proteins (PrP), which in conformationally altered forms are known to cause neurodegenerative diseases in animals as well as humans. Antibodies and nanoparticles were used as mass labels to increase the mass shift and thus amplify the frequency shift signal used in PrP detection. A sandwich assay was used to immobilize PrP between two monoclonal antibodies, one of which was conjugated to the resonator's surface while the other was either used alone or linked to the nanoparticles as a mass label. Without additional mass labeling, PrP was not detected at concentrations below 20 µg/mL. In the presence of secondary antibodies the analytical sensitivity was improved to 2 µg/mL. With the use of functionalized nanoparticles, the sensitivity improved an additional 3 orders of magnitude to 2 ng/mL.Prion proteins (PrP) are transmissible infectious particles, devoid of nucleic acid, that cause fatal neurodegenerative diseases known as bovine spongiform encephalopathy (BSE) in bovine, scrapie (SC) in sheep, and Creutzfeldt-Jakob disease (CJD) in humans. 1 These diseases are caused by genetic, infectious, or sporadic disorders where host-encoded, noninfectious cellular prion proteins (PrP c ) are converted into a conformationally altered, infectious forms designated as PrP sc , PrP CJD , and PrP BSE . 2,3 PrP c is present in abundance in most tissues of the central nervous system. However, posttranslational processes convert PrP c into PrP sc , which leads to altered physiochemical and biochemical properties such as aggregation, insolubility, protease digestion resistance, and a -sheet-rich secondary structure.One such altered property of PrP sc , namely, protease digestion resistance, forms the basis of several diagnostic biochemical tests.To differentiate between PrP c and PrP sc , the sample is pretreated with protease K. Since PrP sc is digestion resistant and PrP c is easily digested by protease K, pretreatment results in a sample that is rich in PrP sc as compared to PrP c . 4,5 Because neither the sensitivity of PrP c nor the resistance of PrP sc to digestion is absolute, the "protease sensitivity assay" cannot definitively measure the presence or absence of PrP.Current prion detection methods employ post mortem analysis after suspicious animals manifest one or more symptoms of the disease. These post mortem tests include gel electrophoresis and western blot, direct-binding and sandwich ELISA, and conformational-dependent immunoassay. [4][5][6] To improve food safety it would be beneficial to screen all the animals for prion disease using ante mortem testing, regardless of the presence of symptoms. Because ante mortem tests could be performed on presymptomatic animals, they would therefore be required to detect extremely small amounts of PrP circulating in blood samples and would have to differentiate PrP c and PP ...

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A biomimetic nanochannel coated with a self-assembled monolayer (SAM) can be used for sensing and analyzing biomolecules. The interaction between a transported biomolecule and a SAM governs the mechanically or electrically driven motion of the molecule. To investigate the translocation dynamics of a biomolecule, we performed all-atom molecular dynamics simulations on a single-stranded DNA in a solid-state nanochannel coated with a SAM that consists of octane or octanol polymers. Simulation results demonstrate that the interaction between DNA and a hydrophobic or a hydrophilic SAM is effectively repulsive or adhesive, respectively, resulting in different translocation dynamics of DNA. Therefore, with proper designs of SAMs coated on a channel surface, it is possible to control the translocation dynamics of a biomolecule. This work also demonstrates that traditional tribology methods can be deployed to study a biological or bio-mimetic transport process.

In this work we study three distinct resonant micromechanical sensor geometries and their ability to detect the addition of material at different locations on the devices. Small regions of gold were patterned on the resonators, and changes in frequency due to the presence of gold were measured as a function of position, device geometry, and the resonant mode. We have demonstrated the conditions under which micromechanical resonators are sensitive to the mechanical properties of added material as well as its mass and have quantified how these qualities have competing effects on resonant frequency using finite element analysis and analytical techniques. In cases where this competition significantly reduces frequency shift amplitudes, localized binding of the analyte is required, and we will compare different sensor designs and their frequency responses. When material is uniformly added to resonators, however, device geometry has little to no effect on sensitivity. While cantilevers may be the most commonly used geometry in this field, we show that they are not necessarily the most sensitive in all situations. In most biosensing applications, flexural rigidity is not expected to have an impact on resonant frequency, suggesting that all available resonator surface area should be used for analyte binding.

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